The Correlation Between The Expression Of PTGDS And Prognosis Of Endometrial Cancer Based On Weighted Gene Co-expression Network Analysis And Immunohistochemical Verification

Objective:To identify key pathogenic genes and reveal the potential molecular mechanisms of endometrial cancer(EC)using bioinformatics analysis and immunohistochemistry validation.Methods:The GSE50830 data set was downloaded from gene expression omnibus(GEO)database.Based on the clinical information of 168 endometrial cancer samples,weighted gene co-expression network analysis(WGCNA)was used to construct the network to search for modules related to EC.GO(Gene ontology)and KEGG(Kyoto Encyclopedia of Gene and Genome)pathway enrichment analyses were performed using the DAVID online tool.Based on Cytohubba plug-in of Cytoscape,the degree of each node in the significance modules was calculated and candidate genes were screened.Differential expression between EC and normal endometrial tissues and prognostic values in EC were analyzed by Oncomine,GEPIA,and Kaplan-Meier Plotter database to determine hub genes.One hub gene was validated by immunohistochemical(IHC)staining of 116 paraffin-embedded endometrial tissues to explore the relationship between their expression and clinicopathological parameters and prognosis of EC patients and their clinical significance.Finally,the genes co-expressed with this hub gene were identified by Linked Omics,its correlation with immune infiltration was evaluated by TIMER to explore the possible biological roles.Results:The top 25%variant genes in the GSE50830 data set were screened to construct a co-expression network,and three modules that were significantly related to tumor cell lines were obtained.The top five nodes ranked by degree in Darkorange,Midnightblue and Blue modules were selected as candidate genes.Among the fifteen candidate genes,four differentially expressed genes were associated with prognosis:The m RNA levels of LGR5 and SST were significantly up-regulated in EC,and the higher the expression level,the worse the prognosis of patients;whereas those of ZNF558 and PTGDS were significantly down-regulated,and the higher the expression level,the better the prognosis of patients.PTGDS was finally determined as the hub gene for further verification.IHC demonstrated that the rates of positive and highly positive expression of PTGDS in EC tissue(56.32%and 37.93%,respectively)were both significantly lower than those in endometrial atypical hyperplasia tissue(82.35%and 64.70%,P=0.045 and 0.041,respectively)as well as in normal endometrial tissue(91.67%and 75.00%,P=0.042 and 0.015,respectively).The overall survival of the low PTGDS expression group was significantly lower than that of the high PTGDS expression group(P=0.002,?(17)=9.515),and its low expression was an independent risk factor for worse prognosis of EC(P=0.044,HR=0.440).Biological function analysis indicated that PTGDS might be involved in the adaptive immune response,leukocyte migration,as well as in the regulation of cell adhesion molecules and chemokine signaling.Additionally,PTGDS expression was positively correlated with immune infiltration status of B cells,CD4~+T cells and macrophages(r=0.227,0.323 and 0.279).Conclusion:LGR5,SST,ZNF558,and PTGDS may participate in the development,progression,and prognosis of EC,in which PTGDS may be a novel biomarker and immunotherapeutic target for EC.