Characterization of m6A Methylation Modification Patterns in Colorectal Cancer Determines Prognosis and Tumor Microenvironment Infiltration

Abstract

Cumulative studies have suggested that dysregulation of m6A regulators and immunity is highly linked to the prognosis of patients with cancer. However, the potential contribution of m6A modification patterns to the tumor microenvironment (TME) and the therapeutic efficacy of immunotherapy for colorectal cancer (CRC) remain elusive. A comprehensive analysis of the m6A modification profiles of 458 patients with CRC was performed by clustering 21 genes encoding m6A methylation regulators and linking the m6A modification pattern with TME characteristics. Using principal component analysis (PCA), a risk model was constructed to quantify individual m6A modification patterns in patients with CRC. The results indicated that the expression profiles and genetic mutations of 21 genes encoding m6A methylation regulators in CRC were characterized by a high degree of heterogeneity. Three m6A clusters had significant differences in prognosis, m6A modification patterns, and TME characteristics. Furthermore, a risk model, termed m6Ascore, was developed by PCA to quality m6A methylation patterns at an individual level. The m6Ascore could stratify patients into high- and low-m6Ascore groups. Further analyses demonstrated that the m6Ascore had a good predictive performance for overall survival and clinical efficacy of immunotherapy in patients with CRC. Finally, the predictive value of the model was validated by external cohorts. In conclusion, the comprehensive characterization of m6A methylation modification patterns might contribute to our understanding of the TME in CRC and the development of personalized antitumor immunotherapy in the future.

Abnormal genetic and epigenetic patterns of m6A regulators associated with tumor microenvironment in colorectal cancer

“…However, the molecular characterization and clinical significance of m6A modifications in human cancers, especially CRC, are just beginning to be explored. In CRC, other researchers provided a comprehensive analysis of four RNA modifications, identified m6A-related mRNA biomarkers related to the clinicopathology and prognosis, and even developed an m6Ascore to predict performance for overall survival and clinical efficacy of immunotherapy ( 36 - 38 ). These studies mainly focused on the influence of m6A regulators themselves on CRC.…”