Exploration of Potential Roles of m5C-Related Regulators in Colon Adenocarcinoma Prognosis

Objectives: The purpose of this study was to investigate the role of 13 m(5)C-related regulators in colon adenocarcinoma (COAD) and determine their prognostic value. Methods: Gene expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) datasets. The expression of m(5)C-related regulators was analyzed with clinicopathological characteristics and alterations within m(5)C-related regulators. Subsequently, different subtypes of patients with COAD were identified. Then, the prognostic value of m(5)C-related regulators in COAD was confirmed via univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The prognostic value of risk scores was evaluated using the Kaplan-Meier method, receiver operating characteristic (ROC) curve. The correlation between the two m(5)C-related regulators, risk score, and clinicopathological characteristics were explored. Additionally, Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Gene Ontology (GO) analysis were performed for biological functional analysis. Finally, the expression level of two m(5)C-related regulators in clinical samples and cell lines was detected by quantitative reverse transcription-polymerase chain reaction and through the Human Protein Atlas database. Results: m(5)C-related regulators were found to be differentially expressed in COAD with different clinicopathological features. We observed a high alteration frequency in these genes, which were significantly correlated with their mRNA expression levels. Two clusters with different prognostic features were identified. Based on two independent prognostic m(5)C-related regulators (NSUN6 and ALYREF), a risk signature with good predictive significance was constructed. Univariate and multivariate Cox regression analyses suggested that the risk score was an independent prognostic factor. Furthermore, this risk signature could serve as a prognostic indicator for overall survival in subgroups of patients with different clinical characteristics. Biological processes and pathways associated with cancer, immune response, and RNA processing were identified. Conclusion: We revealed the genetic signatures and prognostic values of m(5)C-related regulators in COAD. Together, this has improved our understanding of m(5)C RNA modification and provided novel insights to identify predictive biomarkers and develop molecular targeted therapy for COAD.