Construction of cuproptosis-related genes and PD-1 prognostic signature for uterine corpus endometrial carcinoma and analysis of immune infiltration
Objective With a view to find the correlation between prognostic markers of uterine corpus endometrial carcinoma(UCEC)and programmed death 1(PD-1)immune gene,we provide to help for improving the survival and prognosis of patients.Methods The differential expression and clinicopathological characteristics of cuproptosis-related genes in 545 uterine corpus endometrial carcinoma samples and 177 normal samples were analyzed by TCGA database.Survival analysis and gene expression difference analysis were carried out.The genes with high expression related to PD-1 were selected for gene correlation analysis and immune infiltration analysis,and its prognostic risk signature was constructed.Results Among the cuproptosis-related genes,4 genes(ATP7B,SLC31A1,CDKN2A,PDHA1)were up-regulated in uterine corpus endometrial carcinoma,and 4 genes(GLS,MTF1,LIPT1,LIAS)were down-regulated in uterine corpus endometrial carcinoma(P<0.01).PD-1 was significantly correlated with the expression levels of three cuproptosis-related genes(ATP7B,CDKN2A,PDHB)(P<0.01),and was correlated with the expression levels of DLAT,DLD,FDX1,MTF1,PDHA1(P<0.05),but was not correlated with other cuproptosis-related genes.Cuproptosis-related gene CDKN2A was significantly overexpressed in uterine corpus endometrial carcinoma.The expression level of CDKN2A was significantly higher in the advanced cancer group than in the early cancer group.log-rank test was used to compare the prognostic difference between the CDKN2A high expression group and the CDKN2A low expression group.The overall survival of the CDKN2A high expression group was worse than that of the CDKN2A low expression group.Receiver operating characteristic curve(ROC curve)showed that the area under the curve(AUC)for CDKN2A expression predicting 1-,3-,and 5-year survival were 0.614,0.670,and 0.682,respectively.Cox analysis was used to investigate the relationship between CDKN2A expression and overall survival in patients with uterine corpus endometrial carcinoma.Univariate analysis showed age(HR=1.03446,P=0.00061),pTNM stage(HR=1.998,P<0.0001),tumor grade(HR=1.87393,P=0.00016)and CDKN2A expression(HR=1.26224,P<0.0001)were significantly associated with overall survival.Multivariate analysis showed that CDKN2A expression was an independent prognostic factor in patients with uterine corpus endometrial carcinoma(P=0.04214<0.05).Conclusion Cuproptosis-related gene CDKN2A is highly expressed in uterine corpus endometrial carcinoma and affects the prognosis of patients.CDKN2A is closely related to the expression of immune checkpoint gene PD-1 in uterine corpus endometrial carcinoma.CDKN2A is expected to become a potential target for cancer immunotherapy.
CuproptosisUterine corpus endometrial carcinomaCDKN2AProgrammed death 1Immune infiltrationPrognostic signatureTherapeutic target