Construction of Oxidative Stress-Related Genes Risk Model Predicts the Prognosis of Uterine Corpus Endometrial Cancer Patients

SIMPLE SUMMARY: Uterine corpus endometrial carcinoma (UCEC) is the fifth most common malignancy and has become one of the most frequent gynecological cancers in women. In UCEC, a typical symptom of irregular vaginal bleeding usually occurs, leading to the massive release of heme. Then, oxidative stress can be mediated by the degradation products of heme and thus accelerate the development and occurrence of tumors. There are few pieces of research associated with oxidative stress in UCEC. This study aimed to explore the potential link between oxidative stress and UCEC. We discovered 136 oxidative stress-related differentially expressed genes (DEGs) in UCEC, from which we screened 25 prognostic genes significantly related to the overall survival of UCEC patients. Then, a 7-OSRGs-based risk score (H3C1, CDKN2A, STK26, TRPM2, E2F1, CHAC1, MSX1) was generated by Lasso regression. In summary, our results demonstrated that the signature based on OSRGs could serve as a reliable biomarker for predicting the clinical outcome in UCEC. ABSTRACT: Oxidative stress contributes significantly to cancer development. Recent studies have demonstrated that oxidative stress could alter the epigenome and, in particular, DNA methylation. This study aimed to explore the potential link between oxidative stress and uterine corpus endometrial carcinoma (UCEC). An analysis of RNA-seq data and relevant clinical information was conducted with data from The Cancer Genome Atlas (TCGA), and oxidative stress genes were obtained from Gene Set Enrichment Analysis (GSEA). Differentially expressed genes (DEGs) in normal and tumor groups of UCEC were analyzed using GO and KEGG enrichment analysis. As a result of survival analysis, Lasso regression analysis of DEGs, a risk score model of oxidative stress-related genes (OSRGs) was constructed. Moreover, this study demonstrated that OSRGs are associated with immune cell infiltration in UCEC, suggesting oxidative stress may play a role in UCEC development by activating immune cells. We discovered 136 oxidative stress-related DEGs in UCEC, from which we screened 25 prognostic genes significantly related to the overall survival of UCEC patients. BCL2A1, CASP6, GPX2, HIC1, IL19, MSX1, RNF183, SFN, TRPM2 and HIST1H3C are associated with a good prognosis while CDKN2A, CHAC1, E2F1, GSDME, HMGA1, ITGA7, MCM4, MYBL2, PPIF, S100A1, S100A9, STK26 and TRIB3 are involved in a poor prognosis in UCEC. A 7-OSRGs-based risk score (H3C1, CDKN2A, STK26, TRPM2, E2F1, CHAC1, MSX1) was generated by Lasso regression. Further, an association was found between H3C1, CDKN2A, STK26, TRPM2, E2F1, CHAC1 and MSX1 expression levels and the immune infiltrating cells, including CD8 T cells, NK cells, and mast cells in UCEC. NFYA and RFX5 were speculated as common transcription factors of CDKN2A, TRPM2, E2F1, CHAC1, and MSX1 in UCEC.