Background: The 5-methylcytosine (m5C) is one of the important forms of RNA post modification, and its regulatory mechanism in tumors has received increasing attention. However, its potential role in colorectal cancer remains unclear.
Materials and Methods: Here, we systematically investigated the genetic variation and prognostic value of the 14 m5c RNA methylation regulators in colon cancer. The prognostic risk score was constructed using three m5C regulators, which was verified in the GSE17536 (N=177), GSE41258 (N=248) and GSE38832 (N=122) datasets.
Results: The risk score developed from the three-m5C signature represents an independent prognostic factor, which can accurately predict the prognosis of patients with colon cancer in multiple datasets. The cytokine–cytokine receptor interaction and chemokine signaling pathway were significantly enriched in the low-risk score group. Further analysis showed that the three-m5C signature was related to tumor immune microenvironment (TIME), affecting the abundance of tumor-infiltrating immune cells. Especially, patients with low risk score had higher immune score than those with high risk score. In addition, gene set enrichment analysis (GSEA) confirmed that all three regulatory factors are associated with the MAPK/p38 signaling pathway.
Conclusion: In conclusion, our study illustrates that the three-m5C signature may be involved in the regulation of colon cancer immune microenvironment in synergy with the MAPK signaling pathway. Therefore, further studying the three-m5C signature regulatory mechanisms might provide promising targets for improving the responsiveness of colon cancer to immunotherapy.
Keywords: 5-methylcytosine, the three-m5C signature, colon cancer, prognostic, tumor immune microenvironment