Identification of methylation-driven genes prognosis signature and immune microenvironment in uterus corpus endometrial cancer

Abstract

Background Uterus corpus endometrial cancer (UCEC) is the main malignant tumor in gynecology, with a high degree of heterogeneity, especially in terms of prognosis and immunotherapy efficacy. DNA methylation is one of the most important epigenetic modifications. Studying DNA methylation can help predict the prognosis of cancer patients and provide help for clinical treatment. Our research aims to discover whether abnormal DNA methylation can predict the prognosis of UCEC and reflect the patient's tumor immune microenvironment. Patients and methods The clinical data, DNA methylation data, gene expression data and somatic mutation data of UCEC patients were all downloaded from the TCGA database. The MethylMix algorithm was used to integrate DNA methylation data and mRNA expression data. Univariate Cox regression analysis, Multivariate Cox regression analysis, and Lasso Cox regression analysis were used to determine prognostic DNA methylation-driven genes and to construct an independent prognostic index (MDS). ROC curve analysis and Kaplan–Meier survival curve analysis were used to evaluate the predictive ability of MDS. GSEA analysis was used to explore possible mechanisms that contribute to the heterogeneity of the prognosis of UCEC patients. Results 3 differential methylation-driven genes (DMDGs) (PARVG, SYNE4 and CDO1) were considered as predictors of poor prognosis in UCEC. An independent prognostic index was finally established based on 3 DMDGs. From the results of ROC curve analysis and survival curve analysis, MDS showed excellent prognostic ability in TCGA-UCEC. A new nomogram based on MDS and other prognostic clinical indicators has also been successfully established. The C-index of the nomogram for OS prediction was 0.764 (95% CI = 0.702–0.826). GSEA analysis suggests that there were differences in immune-related pathways among patients with different prognosis. The abundance of M2 macrophages and M0 macrophages were significantly enhanced in the high-risk group while T cells CD8, Eosinophils and Neutrophils were markedly elevated in the low-risk group. Meanwhile, patients in the low-risk group had higher levels of immunosuppressant expression, higher tumor mutational burden and immunophenoscore (IPS) scores. Joint survival analysis revealed that 7 methylation-driven genes could be independent prognostic factors for overall survival for UCEC. Conclusion We have successfully established a risk model based on 3 DMDGs, which could accurately predict the prognosis of patients with UCEC and reflect the tumor immune microenvironment.

Establishing a Prognostic Signature Based on Epithelial–Mesenchymal Transition-Related Genes for Endometrial Cancer Patients

“…The IPS was calculated using zscores of representative genes associated with immunogenicity. The IPSs of patients with uterine corpus endometrial carcinoma (UCEC) were extracted from The Cancer Immunome Atlas (TCIA) (https://tcia.at/home) (14).…”

A novel DNA methylation‐driver gene signature for long‐term survival prediction of hepatitis‐positive hepatocellular carcinoma patients

“…DNA methylation is a crucial epigenetic modification type participating a series of biological and pathological processes 7–11 . Aberrant DNA methylation states have been identified in numerous malignant diseases, such as breast cancer, melanoma, colorectal cancer, prostate cancer, and gastric cancer 7,12–17 .…”

“…DNA methylation is a crucial epigenetic modification type participating a series of biological and pathological processes. 7 , 8 , 9 , 10 , 11 Aberrant DNA methylation states have been identified in numerous malignant diseases, such as breast cancer, melanoma, colorectal cancer, prostate cancer, and gastric cancer. 7 , 12 , 13 , 14 , 15 , 16 , 17 Meanwhile, recent studies showed that DNA methylation probes, as well as DNA methylation‐driven genes (MDGs), can be used in the prediction of prognosis, diagnosis and treatment of diseases.…”

Immune Infiltrates of m5C RNA Methylation-Related LncRNAs in Uterine Corpus Endometrial Carcinoma

“…More than 50,000 women worldwide die from UCEC each year [ 2 ]. Currently, surgery combined with radiotherapy and/or chemotherapy is the standard clinical treatment option for patients with UCEC [ 3 ]. Despite the rapid development of modern medicine, the mortality rate of UCEC has continued to increase during recent years, and the prognosis of UCEC patients varies [ 4 ].…”