Gene Alterations of N6-Methyladenosine (m6A)‎ Regulators in Colorectal Cancer: A TCGA Database Study

Abstract EN

N6-methyladenosine (m6A) plays an important role in many cancers.

However, few studies have examined the role of m6A in colorectal CRC.

To examine the effect of m6A on CRC, we studied the genome of 591 CRC cases from The Cancer Genome Atlas (TCGA).

The relationship between the messenger RNA (mRNA) expression, copy number variation (CNVs), and mutations of m6A “Writers,” “Readers,” and “Erasers,” prognosis, immune cell infiltration, and genetic mutations in CRC cases were analyzed.

CNVs and mutations were found in thirteen m6A regulators.

As expected, gain and amplification of m6A regulators increased the mRNA expression of these regulators, while deletion led to reduction in the mRNA expression.

Moreover, CNVs and mutation of these regulators were significantly associated with APC, TP53, and microsatellite instability (MSI) status (p<0.001, p<0.001, and p=0.029, respectively).

CNVs of m6A regulators also correlated with inferred immune cell infiltration in CRC tissues, especially in colon tissues.

Additionally, alterations of RBM15, YTHDF2, YTHDC1, YTHDC2, and METTL14 genes were related to the worse overall survival and disease-free survival (DFS) of CRC patients.

Specifically, the deletion status of “Writers” was also correlated to the DFS of CRC patients (p=0.02).

Gene set enrichment analysis found that FTO was involved in mRNA 3′ end processing, polyubiquitin binding, and RNA polymerase promoter elongation, while YTHDC1 was related to interferon-alpha and gamma response.

In conclusion, a novel relationship was identified between CNVs and mutations of m6A regulators with prognosis and inferred immune function of CRC.

These findings will improve the understanding of the relationship of m6A in CRC.