Clinical Significance Of Expression Of Programmed Cell Death Receptor 1 And Its Ligands In Patients With Endometrial Cancer

Objection:We focused on exploring the clinical significance of expression of PD-1and its ligands in EC patients by detecting the expression of PD-L1 and PD-L2 in EC tissues and the expression of PD-1 in peripheral blood lymphocytes;Construct a network of PD-1 co-expression genes and screen potential biomarkers for PD-1expression in EC by bioinformatics analysis,the genes and pathways participating in PD-1 and regulating the tumor immune status were determined.Method:Part 1: 1)We detected the expression levels of PD-L1 and PD-L2 in 75 EC patients.2)The follow-up results of 75 patients were obtained.3)Analyze the relationship between PD-L1 and PD-L2 and their prognosis and clinicopathological characteristics.Part 2:1)A total of 40 EC patients,40 diagnosed endometrial atypical hyperplasia patients and 40 healthy controls were recruited.The expression level of PD-1 on peripheral blood CD4 + and CD8 + T cells and the proportion of lymphocytes were analyzed by flow cytometry.2)Explore the correlation between the expression level of PD-1 and its clinicopathological characteristics,and then evaluate its clinical value as a biomarker for early diagnosis of EC.Part 3: The EC transcriptomic dataset in TCGA was selected to retrieve gene sets on the c Bio Portal platform,where PD-1 co-expressional genes were acquired.The co-expressional genes were subjected to GO and KEGG enrichment analysis using the DAVID database.The PPI network was then constructed using Cytoscape 3.7.1software and the hub genes were screened.Result: Part 1: 1)PD-L1 and PD-L2 were expressed in the tumor cells and TILs.2)Expression level of PD-L1 is associated with the FIGO stage,differentiation status and histological type of EC.3)PD-L2 expression in TILs is associated with the differentiation status of EC.4)In tumor cells,EC patients with PD-L1 negative expression had a higher survival rate than PD-L1 positive patients.Part 2: 1)On CD4+ and CD8 + T cells,the expression levels of PD-1 in EC and endometrial atypical hyperplasia were significantly higher than that in the control group.Expression levelof PD-1 on CD8 + T cells in EC patients was higher than that in patients with endometrial atypical hyperplasia.2)CD3 +,CD4 + T cells,and CD4 + / CD8 + ratio in peripheral blood of EC patients were significantly higher than healthy controls.3)The expression of CD4 + PD-1 +,CD8 + PD-1 + T cells were valuable for the early diagnosis of EC.4)PD-1 expression on CD4 + T cells was positively associated with FIGO stage and lymph-node metastasis.Part 3: Expression level of PD-1 in EC tissues was significantly higher than that in normal tissues.The survival rate of endometrial cancer patients with high PD-1 expression is higher than that with low PD-1 expression.A total of 976 co-expressed genes were screened out.Enrichment analysis showed that PD-1 co-expressed genes were enriched in membrane components and cell structure.Ten hub genes were obtained by node degree analysis.CD3 E is an important gene related to the prognosis of EC.CD3 E gene is involved in the immune process,and its expression is related to PD-1(Pearson correlation coefficient is 0.82,P<0.01).Those with low CD3 E gene expression in EC have a poor prognosis.Conclusions: The expression level of PD-L1 in EC patients is related to the clinical stage,differentiation status and histological type.The expression of PD-L2 in TILs is related to the differentiation status of EC.In tumor cells,EC patients with PD-L1 negative expression had a higher survival rate than PD-L1 positive patients.The expression of PD-1 was related to the progression of endometrial disease and PD-1expression in peripheral blood T cells may be a new non-invasive biomarkers for early diagnosis of EC.PD-1 co-expression hub genes are related to immunity,among which CD3 E is prognostic marker with the possibility to be involved in PD-1/PD-L1-induced tumor immune escape.This gene provides new clues to study the mechanism and precision target medicine of PD-1/PD-L1 in EC.