Application Value Of PDL1 Detection In Non-small Cell Lung Cancer

Background and Aims:Currently immunotherapy represented by immune checkpoint has been successfully applied in first line and second line of non-small cell lung cancer treatment.Both combination and single agents have a certain incidence of adverse reactions,and a proportion of patients with NSCLC do not benefit from immunotherapy,therefore,in order to enhance the efficiency and avoid adverse reactions,it is very important to select biomarkers to predict the efficacy.The research on the biomarkers of immunotherapy is attractive,including the expression of PDL1,TMB,TILS detection and so on.At present,the expression of PDL1 is widely used in lung cancer research.However,in practice,there are still some problems that have not been solved.Our aim is to find out the problems in the clinical application of PDL1,and to find and provide more evidence for its application.In our study,we selected postoperative lung cancer samples and used different reagents to detect PDL1 in different parts of the samples and some special pathological types of non-small cell lung cancer.Firstly,the effects of different detection reagents22C3 and SP142 and the immunoassay platform on PDL1 detection were identified,and the relationship between PDL1 expression and clinicopathological characteristics and patient prognosis was analyzed.secondly,the heterogeneity of PDL1 expression in different metastatic sites was discussed,and the correlation between heterogeneity and patient prognosis was analyzed.thirdly,we investigated the specificity of PDL1 expression in pulmonary sarcomatoid carcinoma,a specific subtype of NSCLC,and its correlation with immunotherapy,finally,the genes and signal transduction pathways related to PDL1 expression were analyzed by bioinformatics.We are in order to clarify the application value of PDL1 in non-small cell lung cancer.Methods:The first part: assessment of Concordance between 22C3 and SP142 immunohistochemistry assays regarding PD-L1 expression in non small cell lung cancer1.different detection reagents 22C3 and SP142 were used to detect PDL1,and consistency test was used to verify the consistency of the two reagents in detecting PDL12.analysis of the relationship between the test results of different reagents and patients’ overall survival(OS)The second part: conformance assessment of PD-L1 Expression between primary tumour and nodal Metastases in non-small-cell Lung cancer1.PDL1 was detected in different parts of the samples to analyze the consistency of PDL1 expression in different parts of the same patient2.Analysis of the relationship between PDL1 expression in different sites and overall survival(OS)The third part: Correlation of PDL1 expression with clinical features and prognosis in pulmonary sarcomatoid carcinoma1.PDL1 was detected in patients with pulmonary sarcomatoid carcinoma of special subtype of non-small cell lung cancer in our hospital to analyze the specificity of PDL1 expression2.The pulmonary sarcomatoid carcinoma is subdivided to investigate the difference of PDL1 expression between3.Correlation analysis was performed on lung sarcomatoid carcinoma with positive driver genes that received immunotherapy to understand the effect of PDL1 expression on immunotherapyThe fourthpart: The relationship between PDL1 expression and gene expression and related pathways was analyzed1.Transcript data was downloaded from NCCN2.PCA clustering analysis of its rationality3.The KEGG and GO pathways were enriched by differential genesThe fifth part: Weighted Kappa(κ)coefficient and Mc Nemar-Bowker test were used to evaluate the consistency and inconsistency of the test results.SPSS 21.0software was used for statistical analysis.The graphics were generated using Prism Version 7.0Graph Pad).T-test was used for comparison between two groups,and ANOVA was used for comparison between multiple groups.The Kaplan-Meier method was used for survival analysis.Results:The first part: assessment of Concordance between 22C3 and SP142 immunohistochemistry assays regarding PD-L1 expression in non small cell lung cancer1.Clinicopathological characteristics of 135 previous surgical patients in Fujian Tumor Hospita2.The consistency of different reagents in detecting PDL1 was inconsistent,especially in the detection of immune cells.Compared with 22C3,SP142 underestimated the expression of PDL13.Different reagents detected PDL1 with different influencing factors,but there was no significant correlation with the prognosis of patientsThe second part: conformance assessment of PD-L1 Expression between primary tumour and nodal Metastases in non-small-cell Lung cancer1.A total of 76 patients with lymph node metastasis who had been operated on in Fujian Tumor Hospital were analyzed2.PDL1 was detected by 22C3,and the expression of PDL1 was different between primary and metastatic lesions,especially in squamous cell carcinoma3.The expression of PDL1 in primary lesion was not correlated with age,sex,smoking status and pathological type,while the expression of PDL1 in metastatic lesion was correlated with smoking status4.There was no correlation between PDL1 expression and prognosis in either primary or metastatic lesionThe third part: Correlation of PDL1 expression with clinical features and prognosis in pulmonary sarcomatoid carcinoma1.A total of 94 cases of pulmonary sarcoma in cancer hospitals were collected for PDL1 detection,and their clinical pathologic characteristics were summarized2.The expression of PDL1 was different in pulmonary sarcoma patients with oncogene or without oncogene3.Whether the oncogend is positive or negative,PDL1-positive pulmonary sarcoma patients have a certain effect of immunotherapyThe fourthpart:1.Samples and sorting of sample values can be used for subsequent analysis2.PCA clustering analysis indicated that the grouping was reasonable3.PDL1 expression is closely related to genomic expression and related pathwaysConclusion:In our study,we confirmed that the different reagents cannot replace each other,so different detection reagents were used for PDL1 detection,and different immune drugs should be selected for treatment according to the guidance of PDL1.Primary lesion and metastatic lesion of PDL1 expression is different,confirmed expression exists heterogeneity,special type of lung cancer.There are some limitations in using PDL1 to guide immunotherapy.Moreover,the expression of PDL1 is influenced by many factors.Above all,PDL1 as guidance immune checkpoint biomarkers has certain limitation,we need more exploration and accumulate more evidence.