Expression patterns and prognostic value of m⁶A-related genes in colorectal cancer

Colorectal cancer (CRC), including colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ), is one of the most prevalent malignancies worldwide. N⁶-methyladenosine (m⁶A) is a ubiquitous RNA modification that plays a vital role in human tumors, but its expression patterns and prognostic value in CRC have not yet been determined. Here, we first used the Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and the Human Protein Atlas (HPA) databases and a tissue microarray (TMA) cohort to verify the expression of m⁶A-related genes at the mRNA and protein levels. We found that most m⁶A-related genes were substantially upregulated in tumor tissues compared with normal tissues, but METTL14, YTHDF3 and ALKBH5 were downregulated in CRC. There was no obvious difference in FTO. In addition, WTAP, METTL16, HNRNPC and YTHDC1 were abundantly expressed in COAD but not in READ. Moreover, immunofluorescence (IF) analyses of SW480 and HCT116 cells showed that most of the m⁶A-related proteins were expressed in the nucleus and cytoplasm. Survival analysis demonstrated that the expression levels of METTL3, METTL14, METTL16, FTO and ALKBH5 were associated with the clinical outcomes of CRC patients. Taken together, all the results revealed that m⁶A-related genes were dysregulated in CRC and might play a significant role in the progression of CRC.