WO2014190450A1

WO2014190450A1 - Reagent testing kit for aided diagnosis of pulmonary squamous-cell carcinoma patient

Info

Publication number: WO2014190450A1
Application number: PCT/CN2013/000630
Authority: WO
Inventors: 赫捷; 谭锋维; 陈照丽; 孙楠
Original assignee: 中国医学科学院肿瘤医院
Priority date: 2013-05-28
Filing date: 2013-05-28
Publication date: 2014-12-04

Abstract

A reagent testing kit for aided diagnosis of a pulmonary squamous-cell carcinoma, comprising: a product used for detecting protein marker IDH1, a product used for detecting protein marker CA125, a product used for detecting protein marker CYFRA21-1, and a carrier describing the following function: formula I, where X₁ represents the concentration of IDH1, X₂ represents the concentration of CA125, and X₃ represents the concentration of CYFRA21-1. The reagent testing kit has the characteristics of high sensitivity and strong specificity, allows the reliability of a diagnosis result to be far greater than that of employing each of the individual protein markers for diagnosis, and has a significant value and application prospect in diagnosis and treatment of pulmonary squamous-cell carcinoma.

Description

Kit for assisting diagnosis of lung squamous cell carcinoma

The invention relates to a kit for assisting diagnosis of a patient with lung squamous cell carcinoma.

Background technique

Lung cancer is a major disease that seriously threatens human life and health. According to the 2008 global statistics published by the World Health Organization (WHO) International Agency for Research on Cancer (IAHO) in 2008, lung cancer is the leading malignant tumor with the highest morbidity and mortality. The number of new cases worldwide is 1,600,000, and the number of deaths is 1,377,000, accounting for 12.7% and 18.2% of all malignant tumors. According to statistics published by the American Cancer Society, it is estimated that in 2012, the number of new cases of lung cancer in the United States will reach 26,000, and the number of deaths due to lung cancer will reach 160,000. In China, the results of the third national death cause review conducted by the Ministry of Health showed that: lung cancer is the leading cause of death in malignant tumors in the sample area, and the crude death rate is 30.83/100,000, of which 41.34/100,000 are male. Women 19.84/100,000; the first cause of cancer death among men and women. With the acceleration of global aging and the increase of environmental pollution, the incidence of lung cancer will continue to rise. Therefore, the demand for the development of diagnosis and treatment of lung cancer must be more and more intense.

Pathologically, lung cancer can be divided into non-small cell lung cancer (NSCLC, about 85%) and small cell lung cancer (SCLC, about 15%). Among them, NSCLC is mainly composed of squamous cell carcinoma (also known as squamous cell carcinoma or lung squamous cell carcinoma), adenocarcinoma (also known as lung adenocarcinoma) and large cell carcinoma. Squamous and adenocarcinomas each account for 40% of NSCLC.

The incidence of lung cancer is relatively hidden. More than 70% of patients have progressed to the advanced stage at the time of treatment, and surgery has been lost. This is also one of the main reasons for the poor efficacy of lung cancer and high mortality. Therefore, early screening and diagnosis have become the top priority in the prevention and treatment of lung cancer. At present, clinically used lung cancer screening and diagnosis methods are mainly imaging techniques such as chest X-ray examination and CT scanning. Although these imaging data play an important role in diagnosis, there are also many limitations, such as high false positive rate, inability to detect recessive lesions, subclinical lesions, and micrometastatic lesions. In addition, the diagnosis of lung cancer also includes invasive procedures such as bronchoscopy and perforating biopsy. These methods take a long time and increase patient suffering. Therefore, the search for non-invasive, non-radiative, low-cost, rapid diagnosis, sensitive and specific screening and diagnosis methods is an urgent need for early diagnosis of cancer.

A tumor marker refers to a biologically active substance produced by a tumor cell or tissue due to abnormal expression of an oncogene or other tumor-related genes and products thereof, or is itself detached from a cancerous tissue, and is positive There is a certain degree of expression or little yield in often organized or benign diseases. It reflects the occurrence and development of cancer, can be detected in tumor tissue, body fluids and excretion, widely used in the diagnosis of tumors, monitoring recurrence, metastasis, prognosis, predictive efficacy and so on. Several major markers that are widely recognized in clinical practice are: Tumor antigen 125 ( CA125 ) for ovarian cancer, antigen 19-9 (CA19-9) for pancreatic cancer, for colorectal cancer. Carcinoembryonic antigen (CEA) and prostate specific antigen (PSA) for prostate cancer. Other cancers, such as breast and lung cancer, still lack credible tumor markers for screening.

The markers that have been used in the clinical diagnosis of lung cancer are only protein markers, which are the following:

(1) CEA: Gold and Freeman first discovered CEA in colorectal cancer in 1965. It is a glycoprotein with a molecular weight of 180KD and a half-life of 3-4 days. It is an antigen produced during embryonic development and drops significantly after birth. Its specificity is not strong, but it can be used for monitoring tumor development, efficacy judgment and prognosis estimation. It is not sensitive to early diagnosis. Although lung cancer patients have elevated, there are high false negatives and false positives, which are not suitable for lung cancer screening. Used alone in the diagnosis;

(2) CA125: Bast first discovered CA125, a macromolecular glycoprotein with a half-life of about 4. 8 days, mainly used in ovarian cancer, and also in lung cancer.

(3) CYFRA21-1 (CYFRA211): CYFRA211 is a water-soluble fragment of cytokeratin 19 with a half-life of about 4 days;

Although the above protein markers have been used for the diagnosis of lung cancer, their diagnostic efficiency is low and they do not meet clinical needs. Therefore, the development of new diagnostic markers and diagnostic methods can not wait.

IDH1 is a NADP ⁺ -dependent isocitrate dehydrogenase located in the cytoplasm and peroxisomes that catalyzes the oxidative decarboxylation of isocitrate to a-ketoglutarate. The inventors of the present invention have found in previous studies that the levels of IDH1 in patients with lung squamous cell carcinoma and lung adenocarcinoma are significantly higher than those in the normal population and benign lung tumors, and can be used as a new diagnostic marker for lung cancer.

Invention disclosure

It is an object of the present invention to provide a kit for assisting in the diagnosis of a patient with lung squamous cell carcinoma.

The kit for assisting diagnosis of lung squamous cell carcinoma of the present invention includes a product for detecting protein marker IDH1, a product for detecting protein marker CA125, a product for detecting protein marker CYFRA21-1, and a record There are vectors with the following functional formula: P = -

1 + (0.010 * 2.445 ^χ ι * 1.088 ^χ 2 * 2.106 ^χ 3 广 xl represents the concentration of the protein marker IDH1, x2 represents the concentration of the protein marker CA125, and x3 represents the concentration of the protein marker CYFRA21-1.

The protein marker IDH1 may specifically be a protein represented by GENBANK ACCESSION NO. CAG46496. 1 (sequence 1 of the sequence listing; GENBANK ACCESSION NO. CAG46496. 1; 01: 49456351; linear PRI 16-OCT-2008). The protein marker CA125 may specifically be a protein represented by GENBANK ACCESSION NO. AAL65133. 2 (GENBANK ACCESSION NO.

AAL65133. 2; 01 : 24419041; linear PRI 29- OCT- 2002 ). The protein marker CYFRA21-1 may specifically be a protein represented by GENBANK ACCESSION NO. NP-002267. 2 (Sequence Listing 2; 01: 24234699; linear PRI 06- MAY-2012).

The unit of the concentration of the protein marker IDH1 is specifically U/L, the unit of the concentration of the protein marker CA125 is specifically U/mL, and the unit of the concentration of the protein marker CYFRA21-1 is specifically ng/mL.

The following diagnostic criteria can also be recorded on the carrier: When P 0. 738, the patient to be tested is a candidate lung squamous cell carcinoma patient, when? <0. At 738, the patient to be tested was a candidate for non-squamous squamous cell carcinoma.

The present invention also protects a product for detecting the protein marker IDH1, a product for detecting the protein marker CA125, a product for detecting the protein marker CYFRA21-1, and a carrier having a functional formula and a diagnostic standard for preparing a diagnostic lung Application in kits for patients with squamous cell carcinoma:

The function is as follows:

P = -

1 + (0.010 * 2.445 ^χ ι * 1.088 ^χ 2 * 2.106 ^χ 3 广 xl represents the concentration of the protein marker IDH1, the unit is U/L, x2 represents the concentration of the protein marker CA125, the unit is U/mL, x3 represents The concentration of the protein marker CYFRA21-1 is in ng/mL; the diagnostic criteria are as follows:

When P 0. 738, the patient to be tested is a candidate for lung squamous cell carcinoma, when? < 0. 738 The patient to be tested was a candidate for non-squamous squamous cell carcinoma.

The protein marker IDH1 may specifically be a protein represented by GENBANK ACCESSION NO. CAG46496. 1 (sequence 1 of the sequence listing; GENBANK ACCESSION NO. CAG46496. 1; 01: 49456351; linear PRI 16-OCT-2008). The protein marker CA125 can specifically be GENBANK ACCESSION NO. AAL65133. 2 Protein (GENBANK ACCESSION NO.

The product for detecting the protein marker IDH1 according to any of the above may specifically be an IDH1 enzyme-linked immunosorbent assay kit (ELISA Kit; including IDH1 standard) purchased from Wuhan Yousheng Technology Co., Ltd.

The product for detecting the protein marker CYFRA21-1 as described above may specifically be a CYFRA21-1 quantitative assay kit purchased from Roche Diagnostics (Shanghai) Co., Ltd.

The product for detecting the protein marker CA125 according to any of the above may specifically be a CA125 quantitative assay kit of Roche Diagnostics (Shanghai) Co., Ltd.

The invention also protects a method for assisting diagnosis of a patient with lung squamous cell carcinoma, comprising the following steps: (1) separately detecting the concentration of the protein marker IDH1 in the peripheral venous blood of the patient to be tested, the concentration of the protein marker CA125, and the protein marker CYFRA21- Concentration of 1;

(2) Use the following functional formula for auxiliary diagnosis:

P = -

1 + (0.010 * 2.445 ^χ ι * 1.088 ^χ 2 * 2.106 ^χ 3 lou

Xl represents the concentration of the protein marker IDH1, the unit is U/L, x2 represents the concentration of the protein marker CA125, the unit is U/mL, x3 represents the concentration of the protein marker CYFRA21-1, and the unit is ng/mL; At 738, the patient to be tested is a candidate for lung squamous cell carcinoma, when? <0. At 738, the patient to be tested was a candidate for non-squamous squamous cell carcinoma.

The product for detecting the concentration of the protein marker IDH1 may specifically be an IDH1 enzyme-linked immunosorbent assay kit (ELISA Kit; including IDH1 standard) purchased from Wuhan Youersheng Technology Co., Ltd. The product for detecting the concentration of the protein marker CYFRA21-1 may specifically be a CYFRA21-1 quantitative assay kit purchased from Roche Diagnostics (Shanghai) Co., Ltd.

The product for detecting the concentration of the protein marker CA125 may specifically be a CA125 quantitative assay kit of Roche Diagnostics (Shanghai) Co., Ltd.

DRAWINGS

Figure 1 shows the R0C curve of the lung squamous cell carcinoma diagnosis model. The ordinate is sensitivity and the abscissa is specific.

The best way to implement the invention

The following examples are provided to facilitate a better understanding of the invention but are not intended to limit the invention. The experimental methods in the following examples are conventional methods unless otherwise specified. The test materials used in the following examples, unless otherwise specified, were purchased from conventional biochemical reagent stores. In the quantitative tests in the following examples, three replicate experiments were set, and the results were averaged. Sensitivity: The number of cancer patients diagnosed as positive as a percentage of the total number of cancer patients. Specificity: The number of healthy people diagnosed as negative as a percentage of the total healthy population. Example 1. Establishment of the method of the present invention

First, the establishment of the model

There were 489 plasma samples from patients with lung squamous cell carcinoma, and 479 healthy samples from healthy people (normal control). They were taken from patients with lung cancer who were diagnosed by pathology in the Department of Thoracic Surgery, Chinese Academy of Medical Sciences, and the normal population who participated in the cancer screening. The experiment was approved by the ethics committee, and the subjects were informed of the informed consent to sign the informed consent form. Among the patients with lung squamous cell carcinoma, 466 males and 23 females, aged 28-85 years, with an average age of 61 years; in the normal population, 240 males and 239 females, aged 41-70 years, mean age It is 56 years old. Plasma samples were obtained before surgery, and the patients did not receive chemotherapy, radiotherapy, intervention, etc. before.

Data processing using curve expert 1. 4 processing standard curve; GraphPad Pri sm 5. 01 processing Column statistical chart; SPSS 13. 0 for data fitting, establishing mathematical model; SAS 9. 2 for mathematical model testing; MedCalc 9. 6. 2. 0 version calculation model ROC curve and cutoff value; Adobe il lustrator CS3 for image processing.

R0C curve (receiver operat ing characteri ic curve), with sensitivity as the ordinate (Y axis) and specificity as the abscissa (X axis), when giving the test When different cutoffs are used, the corresponding coordinate points are generated, and the curve generated by the continuous line is the R0C curve. The R0C curve can compare the diagnostic efficiency of different tumor markers, and the larger the area under the curve (AUC), the higher the diagnostic efficiency.

The data was analyzed by Logistic binomial regression of SPSS software, and the model was tested using SAS, and a model was finally determined for the diagnosis of lung squamous cell carcinoma. The calculated results of the model were plotted on the R0C curve (Fig. 1). The area under the curve was 0.914 (95% confidence interval: 0.886-0· 938, p<0.0001), and the highest diagnostic marker for lung squamous cell carcinoma, CYFRA21KAUC. Compared to 0.846), there was a significant difference (/ 0.001).

Second, the specific description of the model in step one,

Through the detection of various protein markers in a large number of clinical samples, a large number of data simulations and model establishments were obtained, and the functional formula for assisting diagnosis of lung squamous cell carcinoma was as follows:

p = -

1 + (0.010 * 2.445 ^χ ι * 1.088 ^χ 2 * 2.106 ^χ 3 lou

Xl represents the concentration of the protein marker IDH1 (unit: U/L), x2 represents the concentration of the protein marker CA125 (unit: U/mL), and x3 represents the concentration of the protein marker CYFRA21-1 (unit: ng/mL).

The method for assisting diagnosis of lung squamous cell carcinoma based on the above functional formula is as follows:

(1) Take the peripheral venous blood in the fasting state of the patient to be tested, let stand at room temperature for lh, then centrifuge at 3000 r/min for 15 min, take the supernatant, dispense 1.5 mL EP tube, and store in -80 °C refrigerator.

(2) Detection step (1) The protein marker IDH1 concentration, the protein marker CA125 concentration and the protein marker CYFRA211 concentration in the obtained sample, and then calculate the P value by the above functional formula, and the patient to be tested is candidate when P 0.738 Patients with lung squamous cell carcinoma, when? The patient to be tested at <0.738 was a candidate for non-squamous squamous cell carcinoma. Example 2, verification of the method of the invention

The patients used in this example were 150 patients with clinically diagnosed lung squamous cell carcinoma (peripheral venous blood was obtained before surgery, patients had not received chemotherapy, radiotherapy, intervention, etc.) and 50 healthy people (non-squamous squamous cell carcinoma) Patients), all volunteers with informed consent.

1. Take 5 ml peripheral venous blood in the fasting state of the patient to be tested, let stand for 1 h at room temperature, then centrifuge at 3000 r/min for 15 min, take the supernatant, dispense into two 1.5 mL EP tubes, and store at -80 °C.

2. Dissolve the sample from step 1 for 3 h at room temperature, then centrifuge at 3000 r/min for 5 min.

3. Test the protein marker IDH1 concentration in the sample (supernatant) obtained in step 2 (unit U/L), protein marker CA125 concentration (in U/mL), protein marker CYFRA211 concentration (in ng/mL), and protein marker CEA concentration (in ng/mL).

AAL65133. 2; 01 : 24419041; linear PRI 29- OCT- 2002 ). The protein marker CYFRA21-1 may specifically be a protein represented by GENBANK ACCESSION NO. NP-002267. 2 (sequence 2 of the list; 01: 24234699; linear PRI 06- MAY-2012). The protein marker CEA can specifically be a protein represented by GENBANK ACCESSION NO. CAE75559. 1 (sequence 3 of the sequence listing; GENBANK ACCESSION NO. CAE75559. 1; 01 : 38522495; linear PAT 25-NOV- 2003).

The IDH1 enzyme-linked immunosorbent assay kit (ELISA Kit; including IDH1 standard; catalog number E97839Hu 96T) purchased from Wuhan Youersheng Technology Co., Ltd. was used and the concentration of the protein marker IDH1 was determined according to the instructions of the kit.

The CYFRA21-1 Quantitative Assay Kit (catalog number 11820966122) purchased from Roche Diagnostics (Shanghai) Co., Ltd. was used and the concentration of the protein marker CYFRA21-1 was measured according to the kit instructions.

The concentration of the protein marker CEA was determined using the CEA Quantitative Assay Kit from Roche Diagnostics (Shanghai) Co., Ltd. and following the instructions in the kit (Cat. No. 11731629322).

The CA125 Quantitative Assay Kit (Cat. No. 11776223822) from Roche Diagnostics (Shanghai) Co., Ltd. was used and the concentration of the protein marker CA125 was measured according to the kit instructions.

4. The protein marker IDH1 concentration, the protein marker CA125 concentration, and the protein marker CYFRA21-1 concentration obtained in the step 3 are substituted into the functional formula of the first embodiment to obtain a p value, and the patient is judged to be a lung scale according to the standard of the first embodiment. Cancer patients.

The results of steps 3 and 4 are shown in Tables 1 and 2 (in gender, 1 represents male and 2 represents female). In Tables 1 and 2, the diagnosis results of the respective individual protein markers were used as a control for the results of the diagnosis using the functional formula of Example 1. When the protein marker IDH1 was used alone, according to the conventional threshold, when the concentration was 2.19, the patient to be tested was a candidate lung squamous cell carcinoma patient, and when the concentration was < 2.19, the patient to be tested was a candidate for non-squamous squamous cell carcinoma. When the protein marker CA125 is used alone, as usual Threshold value, when the concentration is 35, the patient to be tested is a candidate lung squamous cell carcinoma patient, and when the concentration is <35, the patient to be tested is a candidate for non-squamous squamous cell carcinoma. When the protein marker CYFRA21-1 was used alone, according to the conventional threshold, when the concentration was 3.3, the patient to be tested was a candidate lung squamous cell carcinoma patient, and when the concentration was <3.3, the patient to be tested was a candidate for non-squamous squamous cell carcinoma. When the protein marker CEA is used alone, according to the conventional threshold, when the concentration is 5, the patient to be tested is a candidate lung squamous cell carcinoma patient, and when the concentration is <5, the patient to be tested is a candidate for non-squamous squamous cell carcinoma.

Table 1 confirmed patients with lung squamous cell carcinoma (+ represents positive diagnosis, - represents negative diagnosis)

122 2 62 0. 533 0. 680652 10. 39 7. 74 + 0. 93366 +

123 1 55 2. 68 0. 661999 4. 96 11. 99 + 0. 99520 +

124 1 56 1. 87 4. 321064 + 34. 75 19. 08 + 1. 00000 +

125 1 54 2. 58 0. 66459 11. 06 2. 81 0. 27184

126 1 76 9. 07 + 0. 5596 21. 55 9. 11 + 0. 98899 +

127 1 71 1. 2 1. 266982 22. 27 4. 2 + 0. 82259 +

128 1 69 6. 87 + 2. 106004 23. 09 58. 16 + 1. 00000 +

129 1 73 2. 54 0. 537559 19. 55 8. 74 + 0. 98260 +

130 1 56 2. 46 1. 490022 18. 19 3. 02 0. 62490

131 1 56 2. 5 2. 417963 + 12. 92 3. 65 + 0. 79653 +

132 1 61 5. 53 + 3. 24415 + 5. 78 1. 91 0. 55114

133 1 67 48. 19 + 2. 124942 30. 56 8. 59 + 0. 99811 +

134 1 63 3. 79 0. 610703 15. 6 6. 92 + 0. 91762 +

135 1 65 4. 34 0. 58519 20. 07 2. 17 0. 31582

136 1 61 16. 75 + 3. 727403 + 19. 21 15. 79 + 0. 99999 +

137 1 56 2. 35 0. 903214 5. 76 3. 69 + 0. 36272

138 1 64 6. 37 + 0. 264687 28. 41 3. 33 + 0. 62428

139 1 59 1. 94 10. 14501 + 101. 2 + 3. 71 + 1. 00000 +

140 1 64 4. 01 0. 067035 14. 03 2. 22 0. 15336

141 1 68 9. 14 + 4. 200955 + 9. 17 3. 51 + 0. 92678 +

142 1 60 1. 34 1. 175483 9. 4 3. 14 0. 39585

143 1 55 0. 663 1. 793961 5. 89 2. 86 0. 40747

144 1 63 3. 06 3. 649472 + 47. 59 + 6. 47 + 0. 99944 +

145 1 55 2. 68 0. 736813 7. 27 5. 44 + 0. 67225

146 1 60 2. 54 1. 338621 14. 79 3. 75 + 0. 65294

147 1 64 4. 33 2. 164235 13. 07 6. 37 + 0. 95994 +

148 1 63 1. 55 0. 438185 34. 77 3. 81 + 0. 82589 +

149 1 45 1. 66 1. 389046 20. 02 5. 38 + 0. 91151 +

150 1 70 1. 02 1. 098302 7. 27 2. 98 0. 31204 Table 2 diagnosed healthy (+ represents positive diagnosis, - represents negative diagnosis) Healthy year CEA IDH1 CA125 CYFRA21-1 Functional person-age concentration diagnosis Concentration diagnosis concentration diagnosis concentration diagnosis P value diagnosis number result result result result

result

The functional formula and diagnostic method of 1 were used to determine the results, and the sensitivity was 66.67% and the specificity was 92%. The protein marker IDH1 and its threshold were used alone to determine the sensitivity, with a sensitivity of 37.33% and a specificity of 92%. Using the protein marker CA125 and its threshold alone, the sensitivity was 16.67% and the specificity was 98%. The protein marker CYFRA21-1 and its threshold were used alone for the determination of sensitivity, the sensitivity was 70.67%, and the specificity was 82%. The protein marker CEA and its threshold were used alone to determine the sensitivity, with a sensitivity of 16.67% and a specificity of 72%. Taking into account the sensitivity and specificity, the functional formula and diagnostic method of Example 1 are significantly superior to the use of several separate protein markers for diagnosis.

Industrial application

Lung cancer ranks first in the world for cancer deaths and is the number one cancer killer that harms the health of our people. Therefore, it is a hot spot in recent years to find tumor markers that can be used for early diagnosis, individual treatment, prognosis and monitoring of recurrence of lung cancer. Using the kit provided by the present invention and assisting diagnosis of lung squamous cell carcinoma according to the corresponding diagnostic criteria, the sensitivity and the specificity are high, and the reliability of the diagnosis is much higher than that of using each individual protein marker for diagnosis. It has great value and application prospect for the diagnosis and treatment of lung squamous cell carcinoma.

Claims

Rights request

1. Kits used to assist in the diagnosis of patients with lung squamous cell carcinoma, including products used to detect the protein marker IDH1, products used to detect the protein marker CA125, products used to detect the protein marker CYFRA21-1, and the records are as follows Functional vector:

P = -

1 + (0.010 * 2.445 ^χ ι * 1.088 ^χ 2 * 2.106 ^χ 3 wide ι

xl represents the concentration of the protein marker IDH1, x2 represents the concentration of the protein marker CA125, and x3 represents the concentration of the protein marker CYFRA21-1.

2. The kit according to claim 1, characterized in that: the protein marker IDH1 is the protein represented by GENBANK ACCESSION NO. CAG46496.1; the protein marker CA125 is the protein represented by GENBANK ACCESSION NO. AAL65133.2 The protein shown is; The protein marker CYFRA21-1 is the protein shown in GENBANK ACCESSION NO. NP-002267.2.

3. The kit according to claim 1 or 2, characterized in that: the concentration unit of the protein marker IDH1 is U/L, the concentration unit of the protein marker CA125 is U/mL, and The concentration unit of protein marker C YFRA21-1 is ng/mL.

4. The kit according to claim 3, characterized in that: the carrier is also recorded with the following diagnostic criteria: When P 0.738, the patient to be tested is a candidate lung squamous cell carcinoma patient, when? When < 0.738, the patient to be tested is a candidate non-lung squamous cell carcinoma patient.

5. Products used to detect the protein marker IDH1, products used to detect the protein marker CA125, products used to detect the protein marker CYFRA21-1 and vectors recorded with functional formulas and diagnostic standards are being prepared to assist in the diagnosis of lung squamous cell carcinoma. Patient Kit Applications:

The functional formula is as follows:

P = -

1 + (0.010 * 2.445 ^χ ι * 1.088 ^χ 2 * 2.106 ^χ 3 wide ι

xl represents the concentration of the protein marker IDH1 in U/L, x2 represents the concentration of the protein marker CA125 in U/mL, x3 represents the concentration of the protein marker CYFRA21-1 in ng/mL; the diagnosis The standards are as follows: When P 0.738, the patient to be tested is a candidate lung squamous cell carcinoma patient. When? When < 0.738, the patient to be tested is a candidate non-lung squamous cell carcinoma patient.

6. The application according to claim 5, characterized in that: the protein marker IDH1 is the protein shown in GENBANK ACCESSION NO. CAG46496.1; the protein marker CA125 is the protein shown in GENBANK ACCESSION NO. AAL65133.2; the protein marker CYFRA21-1 is the protein shown in GENBANK ACCESSION NO. NP-002267.2.

7. A method for assisting the diagnosis of patients with lung squamous cell carcinoma, including the following steps:

(1) Detect the concentration of the protein marker IDH1, the concentration of the protein marker CA125, and the concentration of the protein marker CYFRA21-1 in the peripheral venous blood of the patient to be tested;

(2) Use the following functional formula for auxiliary diagnosis:

P = -

1 + (0.010 * 2.445 ^χ ι * 1.088 ^χ 2 * 2.106 ^χ 3 wide ι

xl represents the concentration of the protein marker IDH1 in U/L, x2 represents the concentration of the protein marker CA125 in U/mL, x3 represents the concentration of the protein marker CYFRA21-1 in ng/mL; when P 0 . When the patient to be tested at 738 is a candidate for lung squamous cell carcinoma? < 0. When 738, the patient to be tested is a candidate non-lung squamous cell carcinoma patient.

8. The method of claim 7, characterized in that: the protein marker IDH1 is the protein represented by GENBANK ACCESSION NO. CAG46496.1; the protein marker CA125 is represented by GENBANK ACCESSION NO. AAL65133.2 The protein; the protein marker CYFRA21-1 is the protein shown in GENBANK ACCESSION NO. NP-002267.2.