JP2018017503A - Evaluation method of lung cancer risk state, lung cancer risk state evaluation device, lung cancer risk state evaluation program, lung cancer risk state evaluation system, and information communication terminal device - Google Patents

Abstract

An object of the present invention is to provide an evaluation method capable of determining a lung cancer risk state with high reliability from cytokine concentration data, and an evaluation device, a program, an evaluation system, and an information communication terminal device used therefor.
The method for evaluating a lung cancer risk state according to the present invention includes a data acquisition step for acquiring cytokine concentration data in a sample collected from an evaluation target, and an evaluation of the lung cancer risk state based on the cytokine concentration data. An evaluation step of substituting the concentration data of the cytokine into a possible risk calculation formula to evaluate the lung cancer risk state in the evaluation target, wherein the data acquisition step includes at least 2 Concentration data of types of cytokines is acquired, and the risk calculation formula includes at least two variables into which at least two types of cytokine concentration values are substituted.
[Selection] Figure 1

Description

  The present invention relates to a lung cancer risk state evaluation method, an evaluation device, a program, an evaluation system, and an information communication terminal device used for evaluating a lung cancer risk state based on cytokine concentration data collected from an evaluation target.

  Ninety percent of deaths in cancer patients are due to cancer metastasis, and those that suppress cancer metastasis are said to suppress cancer. However, diagnostic devices based on morphological information such as CT and MRI that are currently used in clinical practice, and diagnostic devices based on functional information such as PET, have the accuracy required to accurately detect lymph node metastasis less than 1 cm in diameter. I don't have it.

  Cancer metastasis does not occur randomly, with some directivity, such as breast cancer to the lung and colon cancer to the liver. A group of cytokines called chemokines control this organ selectivity. Chemokines have cell migration as the main action, and which cells (lymphocytes) migrate to which organs are strictly controlled by chemokines and their receptors (Non-patent Document 1). In addition, when researched by a literature search engine such as Scopus, 210,000 English academic papers on cancer and cytokines have been published since 1977, and there is a difference between the onset of cancer and the type and concentration of cytokines. It is thought that there is some relation. Furthermore, proposals have been made to use the concentration data of cytokines in body fluids for cancer diagnosis (for example, Patent Documents 1 to 4).

  Although it is not an evaluation of cancer by cytokines, a proposal has been made to evaluate pancreatic cancer using concentration data of two or more types of amino acids in body fluids, and it is related as an analysis method for evaluation in the present invention. Therefore, it referred (patent document 5).

Special table 2014-510517 gazette JP 2013-539857 A JP 2009-513125 A JP 2001-89392 A JP, 2014-1061147, A

Nozomi Koizumi, Yukihiro Nagashima, Biochemistry, Vol. 85, No. 12, December 1099-1101.

  However, the cytokine network responsible for information transmission in vivo is extremely complex, and it is still difficult to determine the lung cancer risk status from cytokine concentration data.

  The present invention has been made in view of the above-described conventional situation, and an evaluation method capable of determining a lung cancer risk state with high reliability from cytokine concentration data, and an evaluation apparatus, program, evaluation system, and information communication terminal used therefor Providing a device is a problem to be solved.

  As a result of examining the concentrations of cytokines in lung cancer and body fluids, the present inventors have found that there is a high correlation between the two. Furthermore, it was found that the risk status of lung cancer can be evaluated with high reliability by using an expression including at least two variables into which the concentration values of at least two cytokines are substituted, and the present invention has been completed. It was.

  That is, the lung cancer risk state evaluation method of the present invention is capable of evaluating a lung cancer risk state based on a data acquisition step for acquiring cytokine concentration data in a sample collected from an evaluation target, and the cytokine concentration data. An evaluation step of substituting the concentration data of the cytokine into a risk calculation formula to evaluate the lung cancer risk state in the evaluation target, wherein the data acquisition step includes at least two types of evaluation methods Cytokine concentration data is acquired, and the risk calculation formula includes at least two variables into which at least two types of cytokine concentration values are substituted.

  According to the present invention, using the concentration data of cytokine obtained from the sample collected from the evaluation object and the risk calculation formula capable of evaluating the lung cancer risk state based on the cytokine concentration data, the value of the formula is calculated. By calculating, the lung cancer risk status in the evaluation target is evaluated. As a result, it is possible to provide highly reliable information that can be helpful in knowing the risk of lung cancer. In addition to improving the reliability of this information, it is also possible to reduce various burdens on the users (for example, mental burden, physical burden, time burden, or financial burden). Play.

  Further, in the lung cancer risk state evaluation method of the present invention, the lung cancer risk state is a degree of possibility that the lung cancer is in the lung cancer. It is possible to evaluate the possibility of having the lung cancer. Further, the lung cancer risk state may include, for example, the degree of lung cancer progression, the degree of possibility of becoming lung cancer in the future, and the like.

  Further, in the lung cancer risk state evaluation method of the present invention, a plurality of categories defined in consideration of at least the degree of possibility of being in the lung cancer risk state, and one or a plurality of threshold values are preset. The evaluation of the degree of possibility that the evaluation target is in the lung cancer risk state means that the evaluation target is classified into any one of the plurality of categories using the value of the risk calculation formula and the threshold value. Is to do. As a result, it is possible to provide highly reliable information that can be helpful in knowing the degree of possibility of being in a lung cancer risk state in an easily understandable form.

  The risk calculation formula in the evaluation method of the present invention is a regression formula, multiple regression formula, fractional formula, linear discriminant formula, formula created by machine learning, formula created by Mahalanobis distance method, canonical discriminant analysis. And any one of the formulas created by the decision tree. As a result, there is an effect that it is possible to further improve the reliability of information that can be used as a reference in knowing the state of the risk of lung cancer.

In the method for evaluating the risk of lung cancer according to the present invention,
The cytokine concentration data include IL-1β, IL-1ra, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, G-CSF, PDGF, MIP -1β, TNF-α, VEGF, Eotaxin, MCP-1 and MIP-1β concentration data of at least two cytokines are included,
The risk calculation formula includes IL-1β, IL-1ra, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, G-CSF, PDGF, MIP It is preferable that at least two variables into which concentration data of at least two cytokines, -1β, TNF-α, VEGF, Eotaxin, MCP-1 and MIP-1β are substituted are included. In this way, the lung cancer risk status can be evaluated with higher reliability. According to the test results of the present inventors, among many types of cytokines, IL-1β, IL-1ra, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10 , IL-12, G-CSF, PDGF, MIP-1β, TNF-α, VEGF, Eotaxin, MCP-1 and MIP-1β concentration data are particularly relevant to lung cancer. Therefore, by evaluating the lung cancer risk status from the concentration data of at least two kinds of these cytokines, the lung cancer risk status can be evaluated with higher reliability.

In the method for evaluating the risk of lung cancer according to the present invention,
A method for evaluating a lung cancer risk state, comprising: a data acquisition step for acquiring cytokine concentration data in a sample collected from an evaluation target; and an evaluation step for evaluating a lung cancer risk state based on the cytokine concentration data,
In the data acquisition step, IL-1β, IL-1ra, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, G-CSF, PDGF, MIP- Concentration data of at least two types of cytokines, 1β, TNF-α, VEGF, Eotaxin, MCP-1 and MIP-1β can be obtained. According to the test results of the present inventors, among many types of cytokines, IL-1β, IL-1ra, IL-5, IL-6, IL-7, IL-8, IL-9, IL- 10, IL-12, G-CSF, PDGF, MIP-1β, TNF-α, VEGF, Eotaxin, MCP-1 and MIP-1β concentration data are particularly relevant to lung cancer. Therefore, by evaluating the lung cancer risk status from the concentration data of at least two kinds of these cytokines, the lung cancer risk status can be evaluated with higher reliability.

Moreover, the lung cancer risk state evaluation apparatus of the present invention is an apparatus for evaluating a lung cancer risk state in an evaluation object, comprising a control unit and a storage unit,
The control unit uses a risk calculation formula capable of evaluating a lung cancer risk state, which is stored in advance in the storage unit, including a variable into which the concentration data of the cytokine to be evaluated and a concentration value of the cytokine are substituted. And an evaluation means for evaluating the lung cancer risk state in the evaluation object by calculating a value of the risk calculation formula,
The cytokine concentration data includes at least two types of cytokine concentration data,
The risk calculation formula includes at least two variables into which at least two types of cytokine concentration values are substituted.

In addition, the lung cancer risk state evaluation method of the present invention includes:
An evaluation method for a lung cancer risk state in an evaluation target, which is executed in an information processing apparatus including a control unit and a storage unit,
Evaluation of the lung cancer risk state stored in advance in the storage unit, including the cytokine concentration data of the evaluation target acquired in advance regarding the concentration value of cytokine and a variable into which the concentration value of cytokine is substituted, executed in the control unit An evaluation step for evaluating the lung cancer risk state in the evaluation target by calculating a value of the risk calculation formula using a risk calculation formula for performing,
The cytokine concentration data includes concentration values of at least two types of cytokines,
The risk calculation formula includes at least two variables into which at least two types of cytokine concentration values are substituted.

In addition, the lung cancer risk state evaluation program of the present invention includes:
A lung cancer risk state evaluation program for evaluating a state of a lung cancer risk state in an evaluation target to be executed in an information processing device including a control unit and a storage unit,
The lung cancer risk state stored in advance in the storage unit, including the cytokine concentration data of the evaluation target acquired in advance relating to the concentration value of cytokine and a variable into which the concentration value of cytokine is substituted for execution in the control unit An evaluation step of evaluating the lung cancer risk state in the evaluation target by calculating a value of the risk calculation formula using a risk calculation formula for evaluation,
The cytokine concentration data includes concentration values of at least two types of cytokines,
The risk calculation formula includes at least two variables into which at least two types of cytokine concentration values are substituted.

In addition, the lung cancer risk state evaluation system of the present invention includes:
A lung cancer risk state evaluation apparatus that includes a control unit and a storage unit, and that evaluates a lung cancer risk state in an evaluation target;
A lung cancer risk state evaluation system comprising a control unit, and an information communication terminal device that provides cytokine concentration data of the evaluation object related to the concentration value of cytokine, and is communicably connected via a network,
The control unit of the information communication terminal device includes:
Cytokine concentration data transmitting means for transmitting the cytokine concentration data of the evaluation object to the lung cancer risk state evaluation device, and an evaluation result for receiving an evaluation result regarding the lung cancer risk state in the evaluation object transmitted from the lung cancer risk state evaluation device Receiving means, and
The control unit of the lung cancer risk state evaluation device includes a cytokine concentration data receiving unit that receives the cytokine concentration data to be evaluated transmitted from the information communication terminal device, and the evaluation received by the cytokine concentration data receiving unit. The evaluation means for evaluating the lung cancer risk state in the evaluation object, which is stored in the storage unit in advance, including variables into which the cytokine concentration data of the object and the concentration value of the cytokine are substituted, and the evaluation means obtained by the evaluation means Evaluation result transmitting means for transmitting the evaluation result to the information communication terminal device,
The cytokine concentration data includes at least two types of cytokine concentration data,
The risk calculation formula includes at least two variables into which at least two types of cytokine concentration values are substituted.

The information communication terminal device of the present invention is
An information communication terminal device that includes a lung cancer risk state evaluation device that evaluates a lung cancer risk state in an evaluation target and a control unit that is communicably connected via a network, and that provides the cytokine concentration data of the evaluation target relating to the concentration value of the cytokine Because
The control unit includes a cytokine concentration data transmitting means for transmitting the cytokine concentration data to be evaluated to the lung cancer risk state evaluation device;
An evaluation result receiving means for receiving an evaluation result relating to the state of the lung cancer risk state in the evaluation object transmitted from the lung cancer risk state evaluation device;
The evaluation result indicates that the lung cancer risk state evaluation device receives the cytokine concentration data of the notation evaluation object transmitted from the information communication terminal device, and receives the cytokine concentration data and cytokine concentration value of the evaluation object received. By calculating a value of the risk calculation formula using a risk calculation formula for evaluating the lung cancer risk state stored in the lung cancer evaluation device in advance including a variable to which is substituted, the lung cancer risk in the evaluation target It is the result of evaluating the state,
The cytokine concentration data includes at least two variables into which concentration values of at least two cytokines are substituted.

In addition, the lung cancer risk state evaluation apparatus of the present invention includes:
Lung cancer comprising an information communication terminal device that provides cytokine concentration data to be evaluated with respect to a cytokine concentration value, a control unit and a storage unit that are communicably connected via a network, and that evaluates the state of lung cancer risk in the evaluation target A risk state assessment device,
The controller is
Cytokine concentration data receiving means for receiving the evaluation target cytokine concentration data transmitted from the information communication terminal device;
Risk calculation for evaluating the state of the lung cancer risk state, which is stored in advance in the storage unit, including variables to which the cytokine concentration data to be evaluated and the cytokine concentration value received by the cytokine concentration data receiving means are substituted. An evaluation means for evaluating the state of the lung cancer risk state in the evaluation object by calculating a value of the risk calculation formula using an expression;
Evaluation result means for transmitting to the information communication terminal device an evaluation result regarding the state of the lung cancer risk state in the evaluation object obtained by the evaluation means,
The cytokine concentration data includes at least two types of cytokine concentration data,
The risk calculation formula includes at least two variables into which at least two types of cytokine concentration values are substituted.

1 is a diagram illustrating a basic principle of Embodiment 1. FIG. FIG. 4 is a diagram showing a time schedule for sample collection in the first embodiment. It is a graph which shows the density | concentration of the healthy subject and the lung cancer patient in the cytokine which showed the significant difference about the blood sample in Example 1. FIG. It is a graph which shows the density | concentration of the healthy subject and the lung cancer patient in the cytokine which showed the significant difference about the saliva sample in Example 1. FIG. It is a graph which shows the density | concentration of the healthy subject and the lung cancer patient in the cytokine which showed the significant difference about the buccal mucosa sample in Example 1. FIG. 3 is a flowchart illustrating an example of a method for evaluating a lung cancer risk state according to the first embodiment. It is a figure which shows an example of the whole structure of this system. It is a block diagram which shows an example of a structure of the lung cancer risk evaluation apparatus 100 of this system.

  Hereinafter, embodiments embodying the present invention will be described. However, the present invention is not limited to the description of this embodiment and the following examples. Various modifications are also included in the present invention as long as those skilled in the art can easily conceive without departing from the scope of the claims.

<Embodiment 1>
The basic principle of Embodiment 1 will be described with reference to FIG. FIG. 1 is a principle configuration diagram showing the basic principle of the first embodiment.

  First, two or more cytokine concentrations of a sample (eg, blood, saliva, buccal mucosa, plasma, serum, sweat, urine, etc.) collected from an evaluation target (animal or human) are measured (step S11).

  In step S11, for example, cytokine concentration data measured by a company or the like that measures the concentration of cytokine may be acquired, or a measurement sample is collected from blood, saliva, or buccal mucosa collected from an evaluation target and measured. May be. The unit of the cytokine concentration data is not particularly limited, and for example, it may be obtained by adding / subtracting / dividing an arbitrary constant to the molar concentration, the weight concentration, or these concentrations.

  Next, the lung cancer risk state in the evaluation target is evaluated using the two or more types of cytokine concentration data acquired in step S11 as an evaluation value for evaluating the lung cancer risk state (step S12).

  According to the evaluation method of the first embodiment, by using a plurality of cytokine concentration data, it provides highly reliable information that can be used as a reference for knowing the lung cancer risk status as compared to the case of using a single cytokine concentration data. can do. In addition to improving the reliability of this information, it is also possible to reduce various burdens on the users (for example, mental burden, physical burden, time burden, or financial burden). Play.

Here, as an evaluation method, a risk calculation formula including two or more types of cytokine concentration data as a variable can be used. Regarding which cytokine is selected, it is preferable to select a cytokine having a high correlation with lung cancer based on the results obtained by examining the correlation between various cytokines and lung cancer patients in advance. Moreover, as a risk calculation formula, for example, a formula of (concentration of cytokine A) + (concentration of cytokine B) can be mentioned. In this way, the assessment of lung cancer risk status can be quantified as a specific numerical value. In addition, weighting may be performed for each type of cytokine based on the results obtained by examining the correlation between various cytokines and lung cancer patients in advance. Furthermore, the value was added using (the value of the concentration data of each cytokine) / (the average value of the concentration data of each cytokine of a person who does not have lung cancer) (or with a certain weight on the value). You may evaluate by a value. In addition, the cytokine concentration value may be corrected according to age, sex, race, presence / absence of oncogene expression, lifestyle, and the like. The degree of these corrections and the presence or absence of correction may be changed depending on the type of cytokine.
The evaluation value obtained as described above may be compared with a general person (for example, the average value of Japanese), and the lung cancer risk state may be indicated by the magnification (see Table 1).

  In addition, when a plurality of categories defined in consideration of at least the degree of possibility of being in a lung cancer risk state and one or a plurality of threshold values are set in advance, in step S12, at least one of the plurality of cytokines. If the concentration value of two cytokines or the concentration value is converted, the evaluation target may be classified into one of a plurality of categories using the converted value and the threshold value, and the formula When the value of or the value of the expression is converted, the evaluation target may be classified into any one of a plurality of categories using the converted value and the threshold value. This makes it possible to provide highly reliable information that can be used as a reference for knowing the degree of possibility of being in a lung cancer risk state in an easily understandable form.

  Here, the concentration values of at least two cytokines of two or more types of cytokines included in the concentration data of cytokines of a plurality of test subjects that are known not to be in a lung cancer risk state (for example, healthy) In the set consisting of, a boundary value when the specificity becomes a predetermined value may be set as the threshold value. In addition, in the set consisting of a plurality of values of the evaluation formula calculated for each test object using the concentration data of the cytokine and the evaluation formula, a boundary value when the specificity becomes a predetermined value is set as a threshold value. Also good.

  In addition, the evaluation formulas are logistic regression formula, fractional formula, linear discriminant formula, multiple regression formula, formula created by support vector machine, formula created by Mahalanobis distance method, formula created by canonical discriminant analysis, decision It can be any one of the expressions created with trees. As a result, it is possible to further improve the reliability of information that can be used as a reference for knowing the state of lung cancer.

In addition, the expression adopted as the evaluation expression means the form of the expression generally used in multivariate analysis. Examples of the expression adopted as the evaluation expression include a fractional expression, multiple regression expression, multiple logistic regression expression, Examples include linear discriminant functions, Mahalanobis distances, canonical discriminant functions, support vector machines, decision trees, and expressions that are expressed as sums of expressions in different forms. Here, in the multiple regression equation, multiple logistic regression equation, and canonical discriminant function, a coefficient and a constant term are added to each variable. The coefficient and the constant term may be real numbers, and more preferably , Any value that belongs to the range of the 99% confidence interval of the coefficient and constant term obtained for performing the various classifications from the data, and more preferably, the value obtained for performing the various classifications from the data. Any value belonging to the range of 95% confidence interval of the coefficient and constant term may be used. In addition, the value of each coefficient and its confidence interval may be a real number multiple thereof, and the value of the constant term and its confidence interval may be obtained by adding / subtracting / dividing any real constant to it. When using display expressions such as logistic regression, linear discrimination, and multiple regression analysis as evaluation expressions, linear conversion (addition of constants, multiple of constants) and monotonic increase (decrease) conversions (such as logit conversion) are evaluated performance. Since this is the same as before conversion, this display expression includes the expression after these conversions are performed.

In the first embodiment, when assessing the risk of lung cancer, two or more types of cytokines for measuring concentration data are used. The cytokine concentration data includes IL-1β, IL-1ra, IL-5, IL-6, IL- 7, IL-8, IL-9, IL-10, IL-12, G-CSF, PDGF, MIP-1β, TNF-α, VEGF, Eotaxin, MCP-1 and MIP-1β Concentration data is included, and the risk calculation formula includes IL-1β, IL-1ra, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12. , G-CSF, PDGF, MIP-1β, TNF-α, VEGF, Eotaxin, MCP-1 and at least two variables to which the concentration data of MIP-1β are substituted are preferably included .
According to the test results of the present inventors, among many types of cytokines, IL-1β, IL-1ra, IL-5, IL-6, IL-7, IL-8, IL-9, IL- 10, IL-12, G-CSF, PDGF, MIP-1β, TNF-α, VEGF, Eotaxin, MCP-1 and MIP-1β concentration data are particularly relevant to lung cancer. Therefore, by evaluating the lung cancer risk status from the concentration data of at least two kinds of these cytokines, the lung cancer risk status can be evaluated with higher reliability.

Example 1
Blood, saliva, and buccal mucosa extracts from 23 healthy men and women and 8 men and women with lung cancer were collected and analyzed for cytokines (27 species). Samples were collected in the morning (7am to 9am), noon (11am to 13pm) and evening (15am to 5pm). In addition, a saliva occult blood test was conducted as a preliminary test before specimen collection (see FIG. 2 and Table 2).

Details of the specimen collection organization, analyzer, cytokine analysis kit, types of cytokines analyzed, and testing methods are shown below.
・ Sample collection organization: Shinshu University Hospital ・ Analyzer: Bio-Plex (Bio-Rad Laboratories)
Cytokine analysis kit: Bio-Plex Pro Human Cytokine 27-Plex
(Bio-Rad Laboratories Co., Ltd.),
・ Test items: IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10,
IL-12P70, IL-13, IL-15, IL-17A, FGF-2, Eotaxin, G-CSF, GM-CSF,
IFN-γ, IP-10, MCP-1, MIP-1α, PDGF-BB, MIP-1β, RANTES,
TNF-α, VEGF
・ Analysis procedure (1) Method for collecting measurement sample from blood 1) Collect a specified amount of blood in a blood collection tube containing 3.2% sodium citrate.
2) Centrifuge and separate the supernatant.
3) Dispense 200 μL of the separated supernatant into microtubes, and divide it into three.
4) Write the ID etc. in a small microtube and store it frozen at -80 ℃.
(2) How to collect a measurement sample from saliva 1) Prepare two collection cups (Nippon Medical: Model No. MS-50) and enter their IDs (the IDs of the two collection cups are the same).
2) Put a 150 μL line into the collection cup.
3) Put the required amount (approximately 150 μL) of saliva into two cups and store them frozen at -80 ° C within 2 hours after collection.
(3) How to collect a measurement sample from the buccal mucosa 1) Take out the collection pad from the buccal mucosa extract collection kit (Intercept, Oral fluid drug test, OraSure Technologies, Inc). With a handle part).
2) Place the sampling pad between the lower gingiva and the buccal mucosa and carefully move it back and forth along the gingiva until the pad is wet.
3) If the sampling pad gets wet, leave it between the gums and the buccal mucosa for 5 minutes.
4) After 5 minutes, carefully open the lid of the container containing the blue liquid and place the sampling pad in the liquid.
5) Fold the handle protruding from the container at the cut and close the lid.
6) After collecting the specimen, transfer the extract collected for storage to a microtube (BIO-BIK: Model No. LT-0200), press the extract that penetrates the collection pad against the tube wall, and squeeze it out. Transfer all of the extract to the microtube.
7) Prepare another microtube for the spare sample, and divide the half into small portions.
8) Write the ID etc. in the microtube and store it frozen at -80 ℃ within 2 hours.

  For samples collected as described above, biomarker analyzer: Bio-Plex (Bio-Rad Laboratories) and cytokine analysis kit: Bio-Plex Pro Human Cytokine 27-Plex (Bio-Rad Laboratories) Was used to measure the concentrations of 27 types of cytokines. In addition, using the statistical analysis software (IBM SPSS Statistics, IBM Japan, Ltd.), Mann-Whitney test was performed on two groups of healthy subjects and lung cancer patients using the analysis results obtained in this way.

<Result>
As described above, 27 types of cytokines were analyzed for samples collected from blood, saliva, and buccal mucosa. As a result, a significant difference of p <0.05 was recognized in the cytokines shown in Table 3.

The results for blood samples, saliva samples, and buccal mucosa samples were as follows.
(About blood samples)
The results are shown in Table 4 and FIG. From these charts, the levels of IL-1ra, Eotaxin, MIP-1β, and VEGF in the blood are higher in lung cancer patients than in healthy individuals, and by measuring the blood levels of these cytokines, It can be seen that lung cancer risk status can be determined. However, these cytokines may also be correlated with cancer risk status other than lung cancer, and in such cases, the reliability of assessment of lung cancer risk status may be reduced. On the other hand, if two or more of these cytokines are measured and evaluated in consideration of the respective results, the risk status of lung cancer can be evaluated with high reliability.

(About saliva samples)
The results are shown in Table 5 and FIG. From these charts, salivary IL-1ra, VEGF, IL-8, IL-1β, G-CSF, TNF-α, IL-7, MIP-1β, IL-12, PDGF, IL-6, IL- The levels of 10 and IL-9 are higher in lung cancer patients than in healthy individuals, and it is clear that lung cancer risk status may be determined by measuring the blood levels of these cytokines. However, these cytokines may also be correlated with cancer risk status other than lung cancer, and in such cases, the reliability of assessment of lung cancer risk status may be reduced. On the other hand, if two or more of these cytokines are measured and evaluated in consideration of the respective results, the risk status of lung cancer can be evaluated with high reliability.

In saliva samples, as shown in Table 6, the concentrations of IL-1β, IL-6, IL-8, G-CSF, IP-10, MIP-1α and MIP-1β increase as the cancer stage progresses. I also found it going up. Therefore, it was suggested that the degree of stage progression could be measured for lung cancer risk status.

(About buccal mucosa sample)
The results are shown in Table 7 and FIG. From these charts, the levels of IL-1ra, IL-1β, MCP-1, MIP-1β, and IL-5 in saliva are higher in lung cancer patients than in healthy individuals, and these cytokines are in the blood. By measuring the concentration, it can be seen that the risk of lung cancer may be determined. However, these cytokines may also be correlated with cancer risk status other than lung cancer, and in such cases, the reliability of assessment of lung cancer risk status may be reduced. On the other hand, if two or more of these cytokines are measured and evaluated in consideration of the respective results, the risk status of lung cancer can be evaluated with high reliability.

(Lung cancer risk status assessment method)
A method for evaluating a lung cancer risk state will be described with reference to the flowchart of FIG. First, the concentration data of the 27 types of cytokines described above in blood, saliva, and buccal mucosa collected from a person who desires an examination are acquired (step S11).

  Next, after removing data such as missing values and outliers from the cytokine concentration data acquired in step S11, the value of the equation is calculated using an equation set in advance as an evaluation equation based on the cytokine concentration data. And evaluate.

<Embodiment 2>
An overview of the second embodiment will be described with reference to FIG. FIG. 6 is a principle configuration diagram showing the basic principle of the second embodiment.
The control unit includes IL-1β, IL-1ra, IL-5, IL-6, IL-7, IL-8, IL-, which are included in the cytokine concentration data of the evaluation target acquired in advance regarding the concentration value of cytokine. 9, IL-10, IL-12, G-CSF, PDGF, MIP-1β, TNF-α, VEGF, Eotaxin, MCP-1 and MIP-1β Formula for evaluating lung cancer risk state, which is stored in advance in the storage unit including variables to be substituted (contains at least two variables into which the concentration values of at least two of the 27 cytokines are substituted) To evaluate the lung cancer risk status in the evaluation target by calculating the value of the expression.

  As described above, according to the second embodiment, the lung cancer risk state in the evaluation target is evaluated by calculating the value of the evaluation formula using the cytokine concentration data to be evaluated and the formula stored in the storage unit as the evaluation formula. As a result, it is possible to provide highly reliable information that can be helpful in knowing the risk of lung cancer.

  Here, the lung cancer risk state may be a degree of possibility of having lung cancer. As a result, it is possible to provide highly reliable information that can serve as a reference in knowing the degree of possibility of having lung cancer.

In addition, it may be determined that the calculated expression value reflects the lung cancer risk state in the evaluation target, and the expression value is converted by, for example, the following method, and the converted value is evaluated. It may be determined that it reflects the lung cancer risk status in the subject. In other words, the value of the expression or the converted value itself may be handled as the evaluation result regarding the lung cancer risk state in the evaluation target. As a result, it is possible to provide highly reliable information that can be helpful in knowing the risk of lung cancer.
For example, an arbitrary value is added / subtracted / divided / divided from / to the value of the evaluation expression so that the possible range of the value of the evaluation expression falls within a predetermined range, or the value of the evaluation expression is converted into a predetermined conversion method (for example, exponential conversion). , Logarithmic transformation, angular transformation, square root transformation, probit transformation, or reciprocal transformation, etc.), and by combining these calculations with the evaluation expression value, the value of the evaluation expression is converted. May be. For example, the value of an exponential function with the value of the evaluation formula as the index and the Napier number as the base (specifically, the natural logarithm ln (p / (1-p)) when the probability p of having lung cancer is defined) (P / (1-p) value in the case where is equal to the value of the evaluation formula), or a value obtained by dividing the calculated exponential function value by the sum of 1 and the value ( Specifically, the value of probability p) may be further calculated.
In addition, the value of the evaluation expression may be converted so that the value after conversion under a specific condition becomes a specific value. For example, the value of the evaluation formula may be converted so that the converted value when the specificity is 80% is 5.0 and the converted value when the specificity is 95% is 8.0. .

  Also, if multiple categories defined with at least the degree of possibility of having lung cancer and one or more thresholds are set in advance, the value of the formula or the value of the formula is converted. In this case, the evaluation target may be classified into any one of a plurality of categories using the converted value and the threshold value. This makes it possible to provide highly reliable information that can be used as a reference for knowing the degree of the possibility of having lung cancer in an easily understandable form.

Next, the configuration of the lung cancer risk evaluation system according to the second embodiment will be described.
First, the overall configuration of this system will be described with reference to FIG. As shown in FIG. 7, the present system includes a lung cancer risk evaluation apparatus 100 that evaluates a lung cancer risk state in an individual to be evaluated, and a client apparatus 200 that provides the individual's cytokine concentration data related to the concentration value of the cytokine (of the present invention). And an information communication terminal device) are communicably connected via the network 300. Furthermore, in addition to the lung cancer risk evaluation apparatus 100 and the client apparatus 200, the present system uses the lung cancer risk state information used when creating an evaluation formula in the lung cancer risk evaluation apparatus 100, and an evaluation used for evaluating the lung cancer risk state. A database apparatus 400 storing equations and the like is configured to be communicably connected via a network 300. Thereby, it becomes reference in knowing the lung cancer risk state from the lung cancer risk evaluation apparatus 100 to the client apparatus 200 or the database apparatus 400 or from the client apparatus 200 or the database apparatus 400 to the lung cancer risk evaluation apparatus 100 via the network 300. Information is provided. Here, the information that is useful for knowing the lung cancer risk state is information about values measured for specific items related to the lung cancer risk state of organisms including humans. In addition, information that is useful for knowing the lung cancer risk state is generated by the lung cancer risk evaluation apparatus 100, the client apparatus 200, and other apparatuses (for example, various measurement apparatuses) and is mainly stored in the database apparatus 400.

  Next, the configuration of the lung cancer risk evaluation apparatus 100 of this system will be described. FIG. 8 is a block diagram showing an example of the configuration of the lung cancer risk evaluation apparatus 100 of the present system, and conceptually shows only the portion related to the present invention in the configuration.

  The lung cancer risk evaluation apparatus 100 is connected to the network 300 via a control unit 102 such as a CPU that centrally controls the lung cancer risk evaluation apparatus, a communication apparatus such as a router, and a communication line such as a dedicated line. The communication interface unit 104 is connected to be communicable, the storage unit 106 stores various databases, tables, files, and the like, and the input / output interface unit 108 connects to the input device 112 and the output device 114. These units are communicably connected via an arbitrary communication path. Here, the lung cancer risk evaluation apparatus 100 may be configured in the same housing as various analysis apparatuses.

  The storage unit 106 is a storage unit, and stores a computer program for giving instructions to the CPU and performing various processes in cooperation with an OS (Operating System). The storage unit 106 includes a user information file 106a, a cytokine concentration data file 106b, a lung cancer risk state information file 106c, a designated lung cancer risk state information file 106d, an evaluation formula related information database 106e, an evaluation result file 106f, Is stored.

The user information file 106a stores user information related to users.
The cytokine concentration data file 106b stores cytokine concentration data relating to the cytokine concentration value.
The lung cancer risk state information file 106c stores lung cancer risk state information used when creating an evaluation formula.

The designated lung cancer risk state information file 106d stores the lung cancer risk state information specified by the lung cancer risk state information specifying unit 102g described later.
The evaluation formula related information database 106e includes a candidate formula file 106e1 for storing a candidate formula created by a candidate formula creation unit 102h1 described later, a verification result file 106e2 for storing a verification result of a candidate formula verification unit 102h2 described later, The selected lung cancer risk state information file 106e3 that stores lung cancer risk state information including the combination of cytokine concentration data selected by the variable selection unit 102h3 to be evaluated, and the evaluation formula file 106e4 that stores the evaluation formula created by the evaluation formula creation unit 102h described later And.

The candidate formula file 106e1 stores candidate formulas created by a candidate formula creation unit 102h1 described later.
The verification result file 106e2 stores the verification result in the candidate formula verification unit 102h2 described later. The information stored in the verification result file 106e2 is configured by associating ranks, candidate formulas, and verification results of each candidate formula (for example, evaluation values of each candidate formula) with each other.

  The selected lung cancer risk state information file 106e3 stores lung cancer risk state information including a combination of cytokine concentration data corresponding to a variable selected by a variable selection unit 102h3 described later. Information stored in the selected lung cancer risk state information file 106e3 includes an individual number, lung cancer risk state index data specified by a lung cancer risk state information specifying unit 102g described later, cytokine concentration data selected by a variable selecting unit 102h3 described later, and , Are related to each other.

  The evaluation formula file 106e4 stores the evaluation formula created by the later-described evaluation formula creation unit 102h. The evaluation result file 106f stores the evaluation result obtained by the evaluation unit 102i described later.

  In addition to the information described above, the storage unit 106 stores various types of Web data for providing the Web site to the client device 200, CGI programs, and the like as other information.

  The communication interface unit 104 mediates communication between the lung cancer risk evaluation device 100 and the network 300 (or a communication device such as a router). That is, the communication interface unit 104 has a function of communicating data with other terminals via a communication line.

  The input / output interface unit 108 is connected to the input device 112 and the output device 114 (hereinafter, the output device 114 may be described as the monitor 114).

  The control unit 102 has an internal memory for storing a control program such as an OS (Operating System), a program defining various processing procedures, and necessary data, and performs various information processing based on these programs. Run.

  The request interpretation unit 102a interprets the request contents from the client device 200 and the database device 400, and passes the processing to each unit of the control unit 102 according to the interpretation result. Upon receiving browsing requests for various screens from the client device 200, the browsing processing unit 102b generates and transmits Web data for these screens. Upon receiving an authentication request from the client device 200 or the database device 400, the authentication processing unit 102c makes an authentication determination. The e-mail generation unit 102d generates an e-mail including various types of information. The Web page generation unit 102e generates a Web page that the user browses with the client device 200.

  The receiving unit 102f receives information (specifically, cytokine concentration data, lung cancer risk status information, evaluation formulas, etc.) transmitted from the client device 200 or the database device 400 via the network 300. The lung cancer risk state information specifying unit 102g specifies target lung cancer risk state index data and cytokine concentration data when creating the evaluation formula.

  The evaluation formula creating unit 102h creates an evaluation formula based on the lung cancer risk status information received by the receiving unit 102f and the lung cancer risk status information specified by the lung cancer risk status information specifying unit 102g. Specifically, the evaluation formula creation unit 102h uses a plurality of candidate formula creation units 102h1, a candidate formula verification unit 102h2, and a variable selection unit 102h3 from the lung cancer risk state information based on the verification results accumulated. An evaluation expression is created by selecting candidate expressions to be adopted as evaluation expressions from the candidate expressions.

  The evaluation unit 102i uses an expression obtained in advance (for example, an evaluation expression created by the evaluation expression creating unit 102h or an evaluation expression received by the receiving unit 102f) and the cytokine concentration data of the individual received by the receiving unit 102f. Use to evaluate lung cancer risk status in an individual by calculating the value of the evaluation formula.

  The result output unit 102 i outputs the processing results (including the evaluation results obtained by the evaluation unit 102 i) in each processing unit of the control unit 102 to the output device 114.

  The transmission unit 102k transmits the evaluation result to the client device 200 that is the transmission source of the cytokine concentration data to be evaluated, or transmits the evaluation formula and the evaluation result created by the lung cancer risk evaluation device 100 to the database device 400. To do.

Next, the configuration of the client device 200 of this system will be described.
The client device 200 includes a control unit, a ROM, an HD, a RAM, an input device, an output device, an input / output, and a communication IF. These units are communicably connected via an arbitrary communication path. .

  The control unit includes a Web browser, an electronic mailer, a reception unit, and a transmission unit. The web browser performs browse processing for interpreting the web data and displaying the interpreted web data on the monitor. The electronic mailer transmits and receives electronic mail according to a predetermined communication protocol. The receiving unit receives various information such as an evaluation result transmitted from the lung cancer risk evaluation apparatus 100 via communication. The transmission unit transmits various information such as individual cytokine concentration data to the lung cancer risk evaluation apparatus 100 via the communication IF.

  The communication IF connects the client device 200 and the network 300 (or a communication device such as a router) so that they can communicate with each other. In other words, the client device 200 is connected to the network 300 via a communication device such as a modem, TA, or router and a telephone line, or via a dedicated line. Thereby, the client apparatus 200 can access the lung cancer risk evaluation apparatus 100 according to a predetermined communication protocol.

  Next, the network 300 of this system will be described with reference to FIG. The network 300 has a function of connecting the lung cancer risk evaluation apparatus 100, the client apparatus 200, and the database apparatus 400 so that they can communicate with each other, such as the Internet, an intranet, or a LAN (including both wired and wireless). The network 300 includes a VAN, a personal computer communication network, a public telephone network (including both analog and digital), a dedicated line network (including both analog and digital), a CATV network, and a mobile line switching network. Or mobile packet switching network (including IMT2000, GSM (registered trademark) or PDC / PDC-P), wireless paging network, local wireless network such as Bluetooth (registered trademark), PHS network, satellite A communication network (including CS, BS, or ISDB) may be used.

Next, the configuration of the database apparatus 400 of this system will be described.
This database apparatus 400 is a lung cancer risk evaluation apparatus 100 or an evaluation expression created by the lung cancer risk evaluation apparatus 100, an evaluation expression created by the lung cancer risk evaluation apparatus 100, and an evaluation performed by the lung cancer risk evaluation apparatus 100. It has a function for storing results and the like. The database device 400 can communicate the database device 400 with a network via a control unit such as a CPU that controls the database device 400 in an integrated manner, a communication device such as a router, and a wired or wireless communication circuit such as a dedicated line. A communication interface unit connected to the PC, a storage unit for storing various databases, tables, files, and the like, and an input / output interface unit connected to the input device and output device. It is connected so that it can communicate via.

  The storage unit is a storage means. For example, a memory device such as a RAM / ROM, a fixed disk device such as a hard disk, a flexible disk, an optical disk, or the like can be used. The storage unit stores various programs used for various processes. The communication interface unit mediates communication between the database device 400 and the network. That is, the communication interface unit has a function of communicating data with other terminals via a communication line. The input / output interface unit is connected to an input device and an output device.

  The control unit has an internal memory for storing control programs such as OS (Operating System), programs that define various processing procedures, and required data, and executes various information processing based on these programs To do. The control unit is roughly divided into a request interpretation unit, a browsing processing unit, an authentication processing unit, an e-mail generation unit, a Web page generation unit, and a transmission unit.

  The request interpretation unit interprets the request content from the lung cancer risk evaluation apparatus 100 and passes the processing to each unit of the control unit according to the interpretation result. Upon receiving browsing requests for various screens from the lung cancer risk evaluation apparatus 100, the browsing processing unit generates and transmits Web data for these screens. The authentication processing unit receives the authentication request from the lung cancer risk evaluation apparatus 100 and makes an authentication determination. The e-mail generator generates an e-mail including various information. The Web page generation unit generates a Web page that the user browses with the client device 200. The transmission unit transmits various information such as lung cancer risk state information and evaluation formulas to the lung cancer risk evaluation apparatus 100.

  Finally, an example of an evaluation formula creation process performed by the lung cancer risk evaluation apparatus 100 will be described. The evaluation formula creation process may be performed by a database device that manages lung cancer risk state information.

  In this description, it is assumed that the lung cancer risk evaluation apparatus 100 stores lung cancer risk state information acquired in advance from the database apparatus 400 in a predetermined storage area of the lung cancer risk state information file 106c. The lung cancer risk evaluation apparatus 100 also stores lung cancer risk state information including lung cancer risk state index data and cytokine concentration data specified in advance by the lung cancer risk state information specifying unit 102g in a predetermined storage area of the specified lung cancer risk state information file 106d. Is stored.

  First, the evaluation formula creation unit 102h creates a candidate formula based on a predetermined formula creation method from the lung cancer risk status information stored in a predetermined storage area of the designated lung cancer risk status information file 106d in the candidate formula creation unit 102h1. Then, the created candidate formula is stored in a predetermined storage area of the candidate formula file 106e1. Next, the evaluation formula creation unit 102h executes various calculations (for example, average and variance) corresponding to the selected formula selection method based on the pancreatic cancer risk state information in the candidate formula creation unit 102h1. Next, the evaluation formula creation unit 102h determines the calculation result and the parameters of the determined candidate formula in the candidate formula creation unit 102h1. Thereby, a candidate formula is created based on the selected formula creation method. Note that when a plurality of different formula creation methods are used in combination to create candidate formulas simultaneously and in parallel (in parallel), the above processing may be executed in parallel for each selected formula creation method. In addition, when creating candidate formulas serially using a combination of different formula creation methods, for example, the lung cancer risk status information is converted using candidate formulas created by performing principal component analysis, and the converted lung cancer Candidate expressions may be created by performing discriminant analysis on the risk state information.

  Next, the evaluation formula creation unit 102h verifies (mutual verification) the candidate formula created by the candidate formula verification unit 102h2 based on a predetermined verification method, and stores the verification result in a predetermined storage area of the verification result file 106e2. . Specifically, the evaluation formula creation unit 102h uses the candidate formula verification unit 102h2 to verify the candidate formula based on the lung cancer risk status information stored in a predetermined storage area of the designated lung cancer risk status information file 106d. The verification data to be used is created, and the candidate expression is verified based on the created verification data.

  Next, the evaluation formula creation unit 102h is included in the lung cancer risk state information used when creating the candidate formula by selecting the variable of the candidate formula based on a predetermined variable selection method by the variable selection unit 102h3. A combination of cytokine concentration data is selected, and lung cancer risk state information including the selected combination of cytokine concentration data is stored in a predetermined storage area of the selected lung cancer risk state information file 106e3.

  Next, the evaluation formula creation unit 102h determines whether or not all combinations of cytokine concentration data included in the lung cancer risk state information stored in the predetermined storage area of the designated lung cancer risk state information file 106d have been completed. If the determination result is “end”, the process proceeds to the next step. If the determination result is not “end”, the process returns to the original step. The evaluation formula creation unit 102h determines whether or not the preset number of times has ended. If the determination result is “end”, the process proceeds to the next step, and the determination result is not “end”. In some cases, you may return to the original step.

  Next, the evaluation formula creation unit 102h determines an evaluation formula by selecting a candidate formula to be adopted as an evaluation formula from a plurality of candidate formulas based on the verification result, and determines the selected evaluation formula (selected candidate formula ) Is stored in a predetermined storage area of the evaluation formula file 106e4.

  The present invention is not limited to the description of the embodiments and examples of the invention described above. Various modifications are also included in the present invention as long as those skilled in the art can easily conceive without departing from the scope of the claims.

S11: Data acquisition step, S12: Evaluation step,
DESCRIPTION OF SYMBOLS 100 ... Lung cancer risk evaluation apparatus 102 ... Control part (102a ... Request interpretation part, 102b ... Browsing process part, 102c ... Authentication process part, 102d ... E-mail production | generation part, 102e ... Web page production | generation part, 102f ... Reception part, 102g ... Lung cancer risk state information designation unit, 102h ... evaluation formula creation unit, 102h1 ... candidate formula creation unit, 102h2 ... candidate formula verification unit, 102h3 ... variable selection unit, 102i ... evaluation unit, 102i1 ... calculation unit, 102i2 ... conversion unit, 102i3 ... generating unit, 102i4 ... classifying unit, 102j ... result output unit, 102k ... transmitting unit)
DESCRIPTION OF SYMBOLS 104 ... Communication interface part 106 ... Memory | storage part (106a ... User information file, 106b ... Cytokine concentration data file, 106c ... Lung cancer risk state information file, 106d ... Designated lung cancer risk state information file, 106e ... Evaluation formula related information database, 106e1 (Candidate expression file, 106e2 ... Verification result file, 106e3 ... Selected lung cancer risk state information file, 106e4 ... Evaluation expression file, 106f ... Evaluation result file)
DESCRIPTION OF SYMBOLS 108 ... Input / output interface part 112 ... Input device 114 ... Output device 200 ... Client device (information communication terminal device)
300 ... Network 400 ... Database device

Claims (11)

A data acquisition step for acquiring cytokine concentration data in a sample collected from the evaluation target;
A lung cancer risk state comprising: an evaluation step for evaluating the lung cancer risk state in the evaluation target by substituting the cytokine concentration data into a risk calculation formula capable of evaluating a lung cancer risk state based on the cytokine concentration data An evaluation method of
In the data acquisition step, concentration data of at least two types of cytokines are acquired,
The method for evaluating a lung cancer risk state, wherein the risk calculation formula includes at least two variables into which at least two kinds of cytokine concentration values are substituted. The lung cancer risk status is the degree of likelihood of being in the lung cancer,
2. The lung cancer risk state evaluation method according to claim 1, wherein the evaluation of the lung cancer risk state in the evaluation target is an evaluation of a possibility that the evaluation target is in the lung cancer. A plurality of categories defined in consideration of at least the degree of possibility of being in the lung cancer risk state, and one or more threshold values are preset,
The evaluation of the degree of possibility that the evaluation target is in the lung cancer risk state means that the evaluation target is classified into one of the plurality of categories using the value of the risk calculation formula and the threshold value. The method for evaluating a lung cancer risk state according to claim 2, wherein The cytokine concentration data include IL-1β, IL-1ra, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, G-CSF, PDGF, MIP -1β, TNF-α, VEGF, Eotaxin, MCP-1 and MIP-1β concentration data for at least two cytokines,
The risk calculation formula includes IL-1β, IL-1ra, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, G-CSF, PDGF, MIP 4. The method according to claim 1, comprising at least two variables into which concentration data of at least two cytokines, -1β, TNF-α, VEGF, Eotaxin, MCP-1 and MIP-1β are substituted. The method for evaluating a lung cancer risk state according to any one of the above items. A data acquisition step for acquiring cytokine concentration data in a sample collected from the evaluation target;
An evaluation step for evaluating a lung cancer risk state based on the cytokine concentration data, and a method for evaluating a lung cancer risk state,
In the data acquisition step, IL-1β, IL-1ra, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, G-CSF, PDGF, MIP- A method for evaluating a lung cancer risk state, comprising obtaining concentration data of at least two types of cytokines, 1β, TNF-α, VEGF, Eotaxin, MCP-1 and MIP-1β. An apparatus for evaluating a lung cancer risk state in an evaluation target,
A control unit and a storage unit;
The control unit uses a risk calculation formula capable of evaluating a lung cancer risk state, which is stored in advance in the storage unit, including a variable into which the concentration data of the cytokine to be evaluated and a concentration value of the cytokine are substituted. And an evaluation means for evaluating the lung cancer risk state in the evaluation object by calculating a value of the risk calculation formula,
The cytokine concentration data includes at least two types of cytokine concentration data,
The lung cancer risk state evaluation apparatus, wherein the risk calculation formula includes at least two variables into which at least two kinds of cytokine concentration values are substituted. An evaluation method for a lung cancer risk state in an evaluation target, which is executed in an information processing apparatus including a control unit and a storage unit,
Evaluation of the lung cancer risk state stored in advance in the storage unit, including the cytokine concentration data of the evaluation target acquired in advance regarding the concentration value of cytokine and a variable into which the concentration value of cytokine is substituted, executed in the control unit An evaluation step for evaluating the lung cancer risk state in the evaluation target by calculating a value of the risk calculation formula using a risk calculation formula for performing,
The cytokine concentration data includes concentration values of at least two types of cytokines,
The method for evaluating a lung cancer risk state, wherein the risk calculation formula includes at least two variables into which at least two types of cytokine concentration values are substituted. A lung cancer risk state evaluation program for evaluating a state of a lung cancer risk state in an evaluation target to be executed in an information processing device including a control unit and a storage unit,
The lung cancer risk state stored in advance in the storage unit, including the cytokine concentration data of the evaluation target acquired in advance relating to the concentration value of cytokine and a variable into which the concentration value of cytokine is substituted for execution in the control unit An evaluation step of evaluating the lung cancer risk state in the evaluation target by calculating a value of the risk calculation formula using a risk calculation formula for evaluation,
The cytokine concentration data includes concentration values of at least two types of cytokines,
A lung cancer risk state evaluation program characterized in that the risk calculation formula includes at least two variables into which at least two kinds of cytokine concentration values are substituted. A lung cancer risk state evaluation apparatus that includes a control unit and a storage unit, and that evaluates a lung cancer risk state in an evaluation target;
A lung cancer risk state evaluation system comprising a control unit, and an information communication terminal device that provides cytokine concentration data of the evaluation object related to the concentration value of cytokine, and is communicably connected via a network,
The control unit of the information communication terminal device includes:
Cytokine concentration data transmitting means for transmitting the cytokine concentration data of the evaluation object to the lung cancer risk state evaluation device, and an evaluation result for receiving an evaluation result regarding the lung cancer risk state in the evaluation object transmitted from the lung cancer risk state evaluation device Receiving means, and
The control unit of the lung cancer risk state evaluation device includes a cytokine concentration data receiving unit that receives the cytokine concentration data to be evaluated transmitted from the information communication terminal device, and the evaluation received by the cytokine concentration data receiving unit. Obtained by the evaluation means for evaluating the lung cancer risk state in the evaluation object, which is stored in the storage unit in advance, including the cytokine concentration data of the object and a variable into which the cytokine concentration value is substituted. Evaluation result transmission means for transmitting the evaluation result to the information communication terminal device,
The cytokine concentration data includes at least two types of cytokine concentration data,
The lung cancer risk state evaluation system, wherein the risk calculation formula includes at least two variables into which at least two kinds of cytokine concentration values are substituted. An information communication terminal device that includes a lung cancer risk state evaluation device that evaluates a lung cancer risk state in an evaluation target and a control unit that is communicably connected via a network, and that provides the cytokine concentration data of the evaluation target relating to the concentration value of the cytokine Because
The control unit includes a cytokine concentration data transmitting means for transmitting the cytokine concentration data to be evaluated to the lung cancer risk state evaluation device;
An evaluation result receiving means for receiving an evaluation result relating to the state of the lung cancer risk state in the evaluation object transmitted from the lung cancer risk state evaluation device;
The evaluation result indicates that the lung cancer risk state evaluation device receives the cytokine concentration data of the notation evaluation object transmitted from the information communication terminal device, and receives the cytokine concentration data and cytokine concentration value of the evaluation object received. By calculating a value of the risk calculation formula using a risk calculation formula for evaluating the lung cancer risk state stored in the lung cancer evaluation device in advance including a variable to which is substituted, the lung cancer risk in the evaluation target It is the result of evaluating the state,
The information communication terminal device, wherein the cytokine concentration data includes at least two variables into which concentration values of at least two cytokines are substituted. Lung cancer comprising an information communication terminal device that provides cytokine concentration data to be evaluated with respect to a cytokine concentration value, a control unit and a storage unit that are communicably connected via a network, and that evaluates the state of lung cancer risk in the evaluation target A risk state assessment device,
The controller is
Cytokine concentration data receiving means for receiving the evaluation target cytokine concentration data transmitted from the information communication terminal device;
Risk calculation for evaluating the state of the lung cancer risk state, which is stored in advance in the storage unit, including variables to which the cytokine concentration data to be evaluated and the cytokine concentration value received by the cytokine concentration data receiving means are substituted. An evaluation means for evaluating the state of the lung cancer risk state in the evaluation object by calculating a value of the risk calculation formula using an expression;
Evaluation result means for transmitting to the information communication terminal device an evaluation result regarding the state of the lung cancer risk state in the evaluation object obtained by the evaluation means,
The cytokine concentration data includes at least two types of cytokine concentration data,
The lung cancer risk state evaluation apparatus, wherein the risk calculation formula includes at least two variables into which at least two kinds of cytokine concentration values are substituted.

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