| Background: The poor differentiation of tumor cells contributes to the rapid progression of uterine corpus endometrial carcinoma(UCEC).Therefore,it is essential to identify candidate genes with the potential to clarify the carcinogenesis and tumor progression mechanisms in UCEC.Methods: We analyzed the gene expression data from the TCGA database to screen genes that affect differentiation,prognosis,and differential expression in UCEC.Least Absolute Selection and Shrinkage Operator(LASSO)regression,univariate Cox and multivariate Cox proportional risk regression analyses were performed to screen out the key gene γ-glutamyl hydrolase(GGH).We then analyzed the prognostic value,clinical relationships of GGH and relevant functions.The relationship between GGH and immune infiltration was assessed by CIBERSORT,EPIC,ss GSEA,unsupervised clustering and immunohistochemistry.In addition,we investigated the effect of GGH knockdown on UCEC cells.Results: We obtained three core genes,GGH,CDKN2 A and SIX1 after gene screening.The impact of GGH was the most obvious on immune infiltration in UCEC.GGH expression was also upregulated in other solid tumors and high level of GGH predicted poor prognosis.A nomogram containing GGH and other clinical features was established and showed a good predictive performance via Decision Curve Analysis(DCA).In the function analysis,we found that GGH affects differentiation,tumor proliferation and immune regulation.The immunosuppressive components were enriched in GGH-high group,with poor efficacy of immunotherapies.The study suggests that GGH may influence the progression of UCEC by regulating the glycolytic process.Conclusions: Our study shows that GGH,a differentiation-associated gene of UCEC,can be used as a diagnostic and prognostic biomarker.It is closely associated with various immune cell infiltrations.Our study elicits the role of GGH on carcinogenesis in uterine corpus endometrial carcinoma. |
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