A better knowledge of the molecular process behind uterine corpus endometrial carcinoma (UCEC) is important for prognosis prediction and the development of innovative targeted gene therapies. The purpose of this research is to discover critical genes associated with UCEC. We analyzed the gene expression profiles of TCGA-UCEC and GSE17025, respectively, using Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis. From four sets of findings, a total of 95 overlapping genes were retrieved. On the 95 overlapping genes, KEGG pathway and GO enrichment analysis were conducted. Then, we mapped the PPI network of 95 overlapping genes using the STRING database. Twenty hub genes were evaluated using the Cytohubba plugin, including NR3C1, ATF3, KLF15, THRA, NR4A1, FOSB, PER3, HLF, NTRK3, EGR3, MAPK13, ARNTL2, PKM2, SCD, EIF5A, ADHFE1, RERGL, TUB, and ENC1. The expression levels of NR3C1, PKM2, and ENC1 were shown to be adversely linked with the survival time of UCEC patients using univariate Cox regression analysis and Kaplan-Meier survival calculation. ENC1 were also overexpressed in UCEC tumor tissues or cell lines, as shown by quantitative real-time PCR and Western blotting. Then we looked into it further and discovered that ENC1 expression was linked to tumor microenvironment and predicted various immunological checkpoints. In conclusion, our data indicate that ENC1 may be required for the development of UCEC and may serve as a future biomarker for diagnosis and therapy.