Lung cancer prognostic markers and their applications

Abstract

The present invention discloses a lung cancer prognostic marker and its application. The present invention discloses that the higher the gene expression of the capsaicin receptor TRPV1 in the cancerous tissue of lung cancer patients, the worse the patient's prognosis. A model influencing the prognosis of lung cancer patients was constructed through multivariate COX survival analysis. The K-M plot curve, ROC curve, and patient survival time all verified the accuracy and specificity of the model. Therefore, the potential application value of this marker as a prognostic indicator in lung cancer can further provide a basis for personalized treatment selection for lung cancer patients, which is of great significance for adopting personalized treatment and reducing lung cancer mortality.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and specifically to a lung cancer prognosis marker and application thereof, and in particular to an application of capsaicin receptor TRPV1 in a lung cancer prognosis marker. Background Art

[0002] Lung cancer is one of the most common malignant tumors worldwide, with the highest mortality rate among all malignant tumors. Metastasis is a key biological process leading to poor prognosis (Siegel RL, Miller KD, Fuchs HF, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021; 71(1):7-33.). Although the five-year survival rate of lung adenocarcinoma patients has gradually increased globally, the five-year survival rate of lung cancer patients in my country is still less than 10%, which is not optimistic.

[0003] Based on histopathological classification, lung cancer can be divided into two major subtypes: small cell lung cancer and non-small cell lung cancer, of which non-small cell lung cancer is more common. Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the two most common subtypes of non-small cell lung cancer. Surgery is the main treatment option for early-stage non-small cell lung cancer, while surgery combined with chemotherapy and / or radiotherapy is the main treatment option for late-stage non-small cell lung cancer. However, despite these treatments, patients' prognosis remains poor, and recurrence after treatment is the main feature of the disease and the main cause of death (Dela Cruz CS, Tanoue LT, Matthay RA. Lung cancer: epidemiology, etiology, and prevention. Clin Chest Med. 2011; 32(4): 605-44.). Therefore, early detection, early treatment, and accurate postoperative monitoring and follow-up are crucial to improving patient survival.

[0004] To date, dozens of abnormal gene expression or protein levels have been identified as being associated with the development and progression of lung cancer. However, there is a lack of sufficient biomarkers to monitor the prognosis of lung cancer patients, especially those in the advanced stage where traditional treatments such as surgical resection are limited. Therefore, the development of novel biomarkers is crucial for monitoring lung cancer prognosis and even for targeted treatment.

[0005] The capsaicin receptor was cloned in 1997 and named because it is activated by capsaicin. Because capsaicin is a vanilloid compound, it is also called the vanilloid receptor (VR1) (Caterina MJ, SCHUMACHER MA, TOMINAGA M, et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature, 1997, 389(6653):816-824.). Because of its ion channel properties, this receptor belongs to the transient receptor potential channel superfamily, hence its standard English name, transient receptor potential vanilloid 1 (TRPV1).Functional expression of TRPV1 has been confirmed in a variety of tumor types, including human breast cancer cell lines (MCF-7 and BT-20), human papillary thyroid carcinoma cell line BCPAP, prostate cancer cell lines (LNCaP and PC-3), urothelial carcinoma cells and gliomas (Sanchez MG, Sanchez AM, Collado B, Malagarie-Cazenave S, Olea N, Carmena MJ, et al. Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue. Eur J Pharmacol. (2005) 515: 20–7. Amantini C, Mosca M, Nabissi M, Lucciarini R, Caprodossi S, Arcella A, et al. Capsaicin-induced apoptosis of glioma cells is mediated by TRPV1 vanilloid receptor and requires p38MAPK activation. J Neurochem. (2007) 102:977–90. Amantini C, Ballarini P, Caprodossi S, Nabissi M, Morelli MB, Lucciarini R, et al. Triggering of transient receptorpotential vanilloid type 1(TRPV1) by capsaicin induces Fas / CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependentmanner. Carcinogenesis. (2009) 30:1320–9. Weber LV, Al-Refae K,. G, Bonatz G, Altmüller J, Becker C, et al. Expression and functionality of TRPV1 in breastcancer cells. Breast Cancer. (2016) 8: 243–52. Xu S, Zhang L, Cheng X, Yu H, Bao J, LuR. Capsaicin inhibits the metastasis of human papillary thyroid carcinoma BCPAP cells through the modulation of the TRPV1 channel. Food Funct. (2018) 9: 344–54.) TRPV1 has been revealed to be associated with many types of cancer, including colorectal cancer, prostate cancer, and pancreatic cancer (Bevan S., Quallo T., Andersson D A TRPV1. Handb Exp Pharmacol. 2014; 222: 207-45. Ramon L, Sebastian B, Gerardo O, Cristián Z, Guillermo V. Thermo TRP channels as modular proteins with allosteric gating. Cell Calcium.2007;42:427-38.Li Li,Cheng Chen,Chengyao Chiang,Tian Xiao,Yangchao Chen,Yongxiang Zhao,Duo Zheng.The Impact of TRPV1 on Cancer Pathogenesis and Therapy: A Systematic Review.Int J BiolSci.2021;17(8):2034-2049.J,Kosmala D,Monika Szopa I,Majchrzak K,BednarczykP.Inflammation,Cancer and Immunity-Implication of TRPV1 Channel.FrontOncol.2019;9:1087.Gao N,Yang F,Chen S,Wan H,Zhao X,Dong H.The role of TRPV1ion channels in the suppression of gastric cancer development. J Exp ClinCancer Res. 2020;39(1):206.Weber LV,Al-Refae K,. G, Bonatz G, Altmüller J, Becker C, et al. Expression and functionality of TRPV1 in breast cancer cells. Breast Cancer. 2016; 8: 243–52. Xu S, Zhang L, Cheng X, Yu H, Bao J, Lu R. Capsaicin inhibits the metastasis of human papillary thyroid carcinoma BCPAP cells through the modulation of the TRPV1 channel. Food Funct. 2018; 9: 344–54.) However, the function of TRPV1 remains highly controversial. TRPV1 expression is upregulated in several natural breast cancers and can slow down breast cancer progression (Weber LV, Al-Refae K, G, Bonatz G, Altmüller J, Becker C, et al. Expression and functionality of TRPV1 in breast cancer cells. Breast Cancer. (2016) 8: 243–52.). Conversely, downregulation of TRPV1 expression is associated with the progression of urothelial carcinoma (Kalogris C, Caprodossi S, Amantini C, Lambertucci F, Nabissi M, Morelli MB, et al. Expression of transient receptor potential vanilloid-1 (TRPV1) in urothelial cancers of human bladder: relation to clinicopathological and molecular parameters. Histopathology. (2010) 57: 744–52.)

[0006] All these findings suggest that the protein encoded by TRPV1 may play an important role in cancer, but the association between TRPV1 and lung cancer progression and its underlying mechanism have not been reported. Therefore, it is of great significance to study and develop genes and / or proteins abnormally expressed in lung cancer for the purpose of prognosis monitoring. Summary of the Invention

[0007] In view of this, the object of the present invention is to provide a lung cancer prognosis marker and application thereof.

[0008] The object of the present invention is achieved through the following technical solutions:

[0009] The present invention provides a use of a capsaicin receptor TRPV1 as a lung cancer prognostic marker in preparing a kit, a detection reagent, a chip, a test paper, a well plate, latex particles or magnetic beads for early diagnosis, risk assessment or prognosis prediction of lung cancer.

[0010] The capsaicin receptor TRPV1 is human capsaicin receptor TRPV1, and the NCBI accession number of the TRPV1 is 7442.

[0011] The kit contains antibodies or fragments thereof that can specifically bind to the protein encoded by the capsaicin receptor TRPV1 gene.

[0012] The gene expression product of the capsaicin receptor TRPV1 includes one or more of the mRNA of the capsaicin receptor TRPV1 or its complementary sequence, the cDNA of the capsaicin receptor TRPV1 or its complementary sequence, the mature protein of the capsaicin receptor TRPV1, and the precursor protein of the capsaicin receptor TRPV1; or any fragment, mutant, derivative or modified product of the above.

[0013] The lung cancer is non-small cell lung cancer.

[0014] The non-small cell lung cancer is lung adenocarcinoma or lung squamous cell carcinoma.

[0015] The present invention also provides a kit for early diagnosis, risk assessment, or prognosis prediction of lung cancer, comprising a molecule expressing mRNA or protein of the capsaicin receptor TRPV1. The capsaicin receptor TRPV1 is human, and the NCBI accession number for TRPV1 is 7442. The kit contains a gene expression product that can specifically detect the capsaicin receptor TRPV1.

[0016] Furthermore, the gene expression product of the capsaicin receptor TRPV1 includes one or more of the mRNA of the capsaicin receptor TRPV1 or its complementary sequence, the cDNA of the capsaicin receptor TRPV1 or its complementary sequence, the mature protein of the capsaicin receptor TRPV1, and the precursor protein of the capsaicin receptor TRPV1; or any fragment, mutant, derivative or modified product of the above.

[0017] Furthermore, the present invention also provides a use of an identification reagent in preparing a product for predicting the prognosis of lung adenocarcinoma, wherein: the identification reagent specifically determines the presence and / or level of the capsaicin receptor TRPV1 gene or its expression product in a subject sample.

[0018] The present invention also provides a use of a capsaicin receptor TRPV1 gene inhibitor in the preparation of a drug for treating lung cancer. The capsaicin receptor TRPV1 gene inhibitor is a molecule or preparation prepared or screened with the TRPV1 gene as a target and has an inhibitory effect on the TRPV1 gene; the NCBI accession number of the TRPV1 is 7442.

[0019] In some embodiments, the subject is a mammal, such as, but not limited to, a human, mouse, rat, guinea pig, rabbit, cow, sheep, horse, camel, pig, dog, cat, monkey, or ape. In some specific embodiments, the mammal is a human.

[0020] In some embodiments, the level is a protein level, particularly for lung adenocarcinoma or lung squamous cell carcinoma; in these embodiments, the identification reagent can identify the protein level based on a quantitative or qualitative immunoassay protocol known in the art, and the immunoassay format may include, but is not limited to, enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), sandwich assay, Western blot, immunoprecipitation, immunohistochemical staining, flow cytometry, fluorescence-assisted cell sorting (FACS), enzyme substrate colorimetric assay, and antigen-antibody aggregation.

[0021] Identification reagents include antibodies or fragments thereof that specifically bind to the protein encoded by the capsaicin receptor TRPV1 gene. Antibodies or fragments thereof of any structure, size, immunoglobulin class, origin, etc. can be used, as long as it binds to the target protein. The antibodies or fragments thereof included in the product of the present invention can be monoclonal or polyclonal. Antibody fragments refer to a portion of an antibody (partial fragment) that retains the binding activity of the antibody to the antigen or a peptide containing a portion of the antibody. Antibody fragments can include F(ab')2, Fab', Fab, single-chain Fv (scFv), disulfide-bonded Fv (dsFv) or its polymers, dimerized V regions (diabodies), or peptides containing CDRs. The identification reagents of the present invention can include isolated nucleic acids encoding the amino acid sequence of the antibody or the antibody fragment, vectors containing the nucleic acid, and cells carrying the vector. In other embodiments, the level is a nucleic acid level, particularly for lung adenocarcinoma; in these embodiments, the identification reagent can function based on known methods using nucleic acid molecules, such as PCR, Southern hybridization, Northern hybridization, dot blot hybridization, fluorescence in situ hybridization (FISH), DNA microarrays, ASO methods, high-throughput sequencing platforms, etc. The products of the present invention can be used to perform qualitative, quantitative, or semi-quantitative analysis.

[0022] In some embodiments, the sample is selected from tumor tissue, for example, tumor tissue obtained or preserved by tissue biopsy, cryopreserved sample, frozen section sample, formalin-preserved tissue, etc.

[0023] In some embodiments, the product of the present invention can be a reagent, a kit, a chip, a test paper, a well plate, latex particles, magnetic beads, etc.

[0024] In some embodiments, prognosis refers to one or a combination selected from the following: prognosis of the outcome of a subject, prognosis of the treatment effect of a subject, and prognosis of the survival of a subject.

[0025] In some specific embodiments, "prognosis" refers to the course or outcome of a cancer patient after tumor growth is suppressed or alleviated by surgery or the like. In this specification, prognosis can be the vital status 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 years, or more, after tumor growth is suppressed or alleviated by surgery. Prognosis can be predicted by detecting the capsaicin receptor TRPV1.

[0026] Prognosis prediction can be performed as follows: based on the fact that the level of the capsaicin receptor TRPV1 gene or its expression product in lung adenocarcinoma patient samples is negatively correlated with the prognosis of lung adenocarcinoma patients, and the level of the capsaicin receptor TRPV1 gene or its expression product in lung squamous cell carcinoma patient samples does not show a correlation with the prognosis of lung squamous cell carcinoma patients, the prognosis of lung adenocarcinoma patients is determined to be good or poor, or the probability of a good or poor prognosis is determined. For example, in this embodiment, quartile analysis can be used to group genes, using the top 25% of expression as the high expression group and the bottom 25% as the low expression group.

[0027] In the present invention, "good prognosis" means that after the patient has suppressed or alleviated the growth of the tumor by surgical treatment, etc., the patient has no critical condition for a long period of time (e.g., 3, 5, 6, 7, 8, 9, 10, 15, 20 years or longer). Alternatively, a good prognosis can mean survival, no metastasis, no recurrence, or no recurrence for such a long time. For example, a good prognosis can mean survival for at least 3 years or especially at least 5 years, preferably without metastasis or recurrence. The most preferred state of a good prognosis is long-term disease-free survival. As used herein, "good prognosis" can also include any such state in which a disease such as metastasis can be found, but the malignancy is low and does not seriously affect viability.

[0028] In the present invention, "poor prognosis" means that a patient develops a fatal condition within a short period of time (e.g., 1, 2, 3, 4, 5 years or less) after tumor growth is suppressed or alleviated by surgical treatment or the like. Alternatively, a poor prognosis means death, metastasis, recurrence, or relapse within such a short period of time. For example, a poor prognosis may mean recurrence, metastasis, or death within at least 3 years, or more particularly, at least 5 years.

[0029] Prognosis is the process of predicting the course or outcome of a patient's condition, and does not imply the ability to predict the course or outcome of a patient's condition with 100% accuracy. Prognosis is the process of determining whether the likelihood of a certain course or outcome has increased, and does not imply determining the likelihood of a certain course or outcome by comparing it to a scenario where the course or outcome does not occur.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] Due to the lack of sufficient biomarkers available to predict the prognosis of patients with lung adenocarcinoma, traditional treatments such as liver transplantation, surgical hepatectomy, and early radiofrequency therapy are limited, especially for patients with advanced lung adenocarcinoma. Therefore, the development of a novel biomarker is crucial for prognostic monitoring and even targeted treatment of lung adenocarcinoma. This paper provides an mRNA for the capsaicin receptor TRPV1 as a prognostic marker for lung adenocarcinoma and establishes a model for predicting the prognosis of patients with lung adenocarcinoma. Finally, the accuracy and specificity of the model were verified using KM plots, receiver operating characteristic (ROC) curves, and patient survival time and status. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Other features, objects and advantages of the present invention will become more apparent upon reading the detailed description of non-limiting embodiments with reference to the following drawings:

[0033] Figure 1 The expression levels of the capsaicin receptor TRPV1 gene in the cancerous and adjacent tissues of patients with lung adenocarcinoma and lung squamous cell carcinoma according to an embodiment of the present invention; wherein N refers to the number of samples;

[0034] Figure 2 The K-Mplot total survival curve of lung cancer patients drawn according to the capsaicin receptor TRPV1 gene expression of an embodiment of the present invention; wherein A is the KM plot total survival curve of lung cancer patients drawn according to the capsaicin receptor TRPV1 gene expression of lung adenocarcinoma patients according to an embodiment of the present invention; B is the KM plot total survival curve of lung adenocarcinoma patients drawn according to the capsaicin receptor TRPV1 gene expression of lung adenocarcinoma patients according to an embodiment of the present invention; C is the KM plot total survival curve of lung squamous cell carcinoma patients drawn according to the capsaicin receptor TRPV1 gene expression of lung squamous cell carcinoma patients according to an embodiment of the present invention;

[0035] Figure 3 The difference in protein levels between cancerous tissue and normal tissue of lung cancer patients is shown in Figure 1, where A is lung adenocarcinoma; B is lung squamous cell carcinoma;

[0036] Figure 4 A K-Mplot overall survival curve of lung cancer patients was drawn for the capsaicin receptor TRPV1 protein expression level according to Example 4 of the present invention; wherein A represents lung adenocarcinoma, B represents lung squamous cell carcinoma, and N represents the number of samples. DETAILED DESCRIPTION

[0037] The present invention will be described in detail below with reference to the examples. The following examples will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that those skilled in the art may make several adjustments and improvements without departing from the scope of the present invention. These all fall within the scope of protection of the present invention.

[0038] Example 1 Screening for lung cancer prognostic biomarkers

[0039] 1. Determination of Capsaicin Receptor TRPV1 Gene Expression Level

[0040] In this example, we analyzed the gene expression of the capsaicin receptor TRPV1 in various cancers using the TIMER platform (Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, et al. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res. 2017; 77:e108-10.) and compared the expression levels in cancer and normal tissues. The thresholds were set as follows: p-value of 1E-6, fold change of 2, and gene ranking in the top 5%.

[0041] 2. Prognostic analysis of patients with lung adenocarcinoma and squamous cell lung carcinoma

[0042] The relationship between TRPV1 gene expression and survival in lung adenocarcinoma and squamous cell lung carcinoma was determined by PrognoScan and GEPIA2 (Hideaki Mizuno, Kunio Kitada, Kenta Nakai and Akinori Sarai. PrognoScan: a new database for meta-analysis of the prognostic value of genes. BMC Medical Genomics. 2009; 2: 18. Tang, Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019; 47(W1): W556-60.). The threshold was adjusted to a Cox p-value of < 0.05.

[0043] 3. Statistical Analysis

[0044] Results generated by TIMER are presented as p-values and fold changes. Results from PrognoScan, Kaplan-Meier plots, and GEPIA are presented as HRs and p / Cox p-values. Correlation coefficients for gene expression were analyzed, and p-values < 0.05 were considered statistically significant. Kaplan-Meier plots and corresponding log-rank tests were used to assess differences in OS between groups.

[0045] Example 2: Difference in expression of capsaicin receptor TRPV1 between cancerous tissue and normal tissue of lung adenocarcinoma patients

[0046] To evaluate the expression of capsaicin receptor TRPV1 in patients with lung adenocarcinoma, this example used RNA sequencing data of lung adenocarcinoma from TCGA to analyze the gene expression of capsaicin receptor TRPV1. The differential expression of capsaicin receptor TRPV1 gene between cancer tissues and adjacent normal tissues of patients with two subtypes of lung cancer (adenocarcinoma and squamous cell carcinoma) was studied. Figure 1 As shown. The gene expression of capsaicin receptor TRPV1 in the cancer tissues of patients with lung adenocarcinoma was significantly lower than that in normal tissues, and no significant difference was found in patients with lung squamous cell carcinoma ( Figure 1 ).

[0047] The capsaicin receptor TRPV1 is a protein expressed on the cell membrane. The protein level is different between the cancerous tissue and normal tissue of lung cancer patients. In this example, it can be seen that the staining is concentrated on the cell membrane. The capsaicin receptor TRPV1 level in cancer tissue is generally low or even undetectable, lower than that in normal tissue ( Figure 3 ).

[0048] Example 3 Relationship between capsaicin receptor TRPV1 gene expression and prognosis of lung adenocarcinoma patients

[0049] This example analyzes the relationship between capsaicin receptor TRPV1 gene expression and lung cancer prognosis. Based on Affymetrix microarray and RNA sequencing data, the Kaplan-Meier Plotter database was used to determine the relationship between capsaicin receptor TRPV1 and lung cancer prognosis.

[0050] like Figure 2As shown, A is a KM plot total survival curve of lung cancer patients drawn according to the capsaicin receptor TRPV1 gene expression of lung adenocarcinoma patients according to an embodiment of the present invention; B is a KM plot total survival curve of lung adenocarcinoma patients drawn according to the capsaicin receptor TRPV1 gene expression of lung adenocarcinoma patients according to an embodiment of the present invention; C is a KM plot total survival curve of lung squamous cell carcinoma patients drawn according to the capsaicin receptor TRPV1 gene expression of lung squamous cell carcinoma patients according to an embodiment of the present invention; It can be seen that in this embodiment, the capsaicin receptor TRPV1 gene expression level is high and the prognosis of lung cancer patients is poor ( Figure 2 Figure A). Among the subtypes of lung cancer, the higher the TRPV1 gene expression, the shorter the overall survival of lung adenocarcinoma patients. That is, the higher the TRPV1 gene expression, the worse the prognosis of lung cancer patients ( Figure 2 However, no significant negative correlation was found in patients with lung squamous cell carcinoma ( Figure 2 (Figure C in the middle).

[0051] Example 4 Effect of capsaicin receptor TRPV1 protein levels on the prognosis of patients with lung adenocarcinoma and squamous cell carcinoma

[0052] In order to verify the role of capsaicin receptor TRPV1 protein in the development and progression of lung adenocarcinoma, this example studies the effect of capsaicin receptor TRPV1 protein on the prognosis of patients with lung adenocarcinoma and squamous cell carcinoma in vitro.

[0053] A total of 197 patients with lung adenocarcinoma and squamous cell carcinoma were enrolled. Based on the completeness of experimental data, pathological information, and prognostic information, 78 patients with lung adenocarcinoma and 80 patients with squamous cell carcinoma were selected for the confirmatory analysis. Surgically resected cancerous tissue and adjacent paracancerous tissue were collected, embedded in paraffin, and prepared into tissue microarrays. Immunohistochemical staining was performed on the microarrays, and the results were scored and interpreted. TRPV1 protein levels were also analyzed to assess the prognosis of patients with lung adenocarcinoma and squamous cell carcinoma. During the 60-month follow-up period after surgery, 30 of the 78 patients with lung adenocarcinoma survived and 48 died, of whom 41 had high TRPV1 expression and 33 had low TRPV1 expression. Twenty-nine of the 80 patients with squamous cell carcinoma survived and 51 died, of whom 31 had high TRPV1 expression and 46 had low TRPV1 expression.

[0054] Statistical Analysis: The tissue microarray interpretation method for patients with lung adenocarcinoma and squamous cell carcinoma is as follows: First, the overall staining is examined to determine the location, intensity, and location of staining. In this example, the degree of staining is assessed by comparison with the stroma and can be categorized into three levels: 1-3, with 1 representing mild staining, 2 representing moderate staining, and 3 representing severe staining. This judgment can be made based on the overall staining. Next, the percentage of positively stained cells is considered 1 for 0-25%, 2 for 26-50%, 3 for 51-75%, and 4 for 75% and above. The staining score is calculated by multiplying the staining intensity by the percentage of positive cells. A score of 0-3 indicates low expression, 4-5 indicates moderate expression, and 6 and above indicates high expression. Statistical analysis is then performed as follows: the staining scores are grouped into low- to medium-expression, high-expression, and so on, and then correlated with the patient's survival period to generate a survival curve. The staining scores are grouped into low- to medium-expression, high-expression, and so on, and then compared between the two groups to produce a single result. By grouping the staining scores into low- to medium-expression, high-expression groups, and tabulating them with the patient's TNM stage, a result can be obtained. By grouping the staining scores into low- to medium-expression, high-expression groups, and tabulating them with the patient's differentiation, a result can be obtained. By grouping the staining scores into low- to medium-expression, high-expression groups, and tabulating them with the patient's other indicators, a result can be obtained.

[0055] like Figure 4 The figure shows the K-Mplot overall survival curve of lung cancer patients drawn based on the expression level of capsaicin receptor TRPV1 protein in this example, where A is lung adenocarcinoma and B is lung squamous cell carcinoma. This example analyzes the relationship between TRPV1 protein levels and prognosis in patients with lung adenocarcinoma and lung squamous cell carcinoma, and concludes that high TRPV1 protein levels are associated with poor prognosis in both types of lung cancer patients ( Figure 4 A picture and Figure 4 (Figure B).

[0056] In summary, the gene expression level and protein level of TRPV1 in the present invention have guiding significance for the prognosis of patients with lung adenocarcinoma ( Figure 2 Figure C and Figure 4 A), TRPV1 protein level has guiding significance for the prognosis of patients with lung squamous cell carcinoma ( Figure 4 The present invention effectively overcomes the shortcomings of the prior art and has high industrial utilization value.

[0057] Unless otherwise stated, the experimental methods, detection methods, and preparation methods disclosed in the present invention all adopt conventional techniques in molecular biology, biochemistry, chromatin structure and analysis, analytical chemistry, cell culture, recombinant DNA technology, and related fields in the art.

[0058] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art may make various variations or modifications within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. Use of a reagent for detecting the expression of capsaicin receptor TRPV1 protein in the preparation of a kit or detection reagent for predicting the prognosis of lung cancer; the lung cancer is squamous cell lung carcinoma.

2. The use according to claim 1, characterized in that , the capsaicin receptor TRPV1 is human capsaicin receptor TRPV1, and the NCBI accession number of the TRPV1 is 7442.

3. The use according to claim 1, characterized in that The kit contains antibodies or fragments thereof that can specifically bind to the protein encoded by the capsaicin receptor TRPV1 gene.

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