5mC-Related lncRNAs as Potential Prognostic Biomarkers in Colon Adenocarcinoma

SIMPLE SUMMARY: To identify the prognostic significance of 5mC-related lncRNAs in colon adenocarcinoma (COAD), we examined the expression levels and mutations of 21 5mC-regulated genes of COAD in TCGA. We also identified lncRNAs associated with 5mC regulatory genes using Pearson correlation analysis. After the least absolute shrinkage and selection operator (Lasso) Cox regression, the risk signature of 4 5mC-related lncRNAs was selected. Next, the risk signature’s predictive efficacy was proven. Moreover, the biological mechanism and potential immunotherapeutic response of this risk signature were identified. Collectively, we constructed the 5mC-related lncRNA risk signature, which could provide a novel prognostic prediction of COAD patients. ABSTRACT: Globally, colon adenocarcinoma (COAD) is one of the most frequent types of malignant tumors. About 40~50% of patients with advanced colon adenocarcinoma die from recurrence and metastasis. Long non-coding RNAs (lncRNAs) and 5-methylcytosine (5mC) regulatory genes have been demonstrated to involve in the progression and prognosis of COAD. The goal of this study was to explore the biological characteristics and potential predictive value of 5mC-related lncRNA signature in COAD. In this research, The Cancer Genome Atlas (TCGA) was utilized to obtain the expression of genes and somatic mutations in COAD, and Pearson correlation analysis was used to select lncRNAs involved in 5mC-regulated genes. Furthermore, we applied univariate Cox regression and Lasso Cox regression to construct 5mC-related lncRNA signature. Then Kaplan–Meier survival analysis, principal components analysis (PCA), receiver operating characteristic (ROC) curve, and a nomogram were performed to estimate the prognostic effect of the risk signature. GSEA was utilized to predict downstream access of the risk signature. Finally, the immune characteristics and immunotherapeutic signatures targeting this risk signature were analyzed. In the results, we obtained 1652 5mC-related lncRNAs by Pearson correlation analysis in the TCGA database. Next, we selected a risk signature that comprised 4 5mC-related lncRNAs by univariate and Lasso Cox regression. The prognostic value of the risk signature was proven. Finally, the biological mechanism and potential immunotherapeutic response of the risk signature were identified. Collectively, we constructed the 5mC-related lncRNA risk signature, which could provide a novel prognostic prediction of COAD patients.