Characterization of m6A methylation modifications in gastric cancer.

ABSTRACT

Widely recognized as an essential epitranscriptomic modification, RNA N6-methyladenosine (m6A) is involved in both physiological and pathological processes. Here, we want to investigate m6A modification's potential roles in gastric cancer. Gastric cancer samples were selected from TCGA-STAD and GEO (GSE84426, GSE84433) datasets. Based on 18 regulators of m6A, m6A modification patterns were thoroughly evaluated in gastric cancer samples. Principal component analysis algorithms were used to construct the m6Ascore, using which, m6A modification features in tumor somatic mutations and immune checkpoint blockade therapy were analyzed. 34 gastric cancer samples were collected to verify the effectiveness of the m6Ascore. Here, we determined three different m6A modification patterns. m6Acluster-C modification pattern presented immune activation-associated enrichment pathways and have significant survival advantages. Then, in gastric cancer, m6Ascore could act as an independent prognostic biomarker. A significant survival benefit was exhibited in patients with high m6Ascore. Moreover, the modification signature of m6A uncovered in this study would help to predict immune checkpoint blockade therapy's responses. In conclusion, our discoveries all pointed to the fact that modification patterns of m6A were linked to the TME. Moreover, evaluation of individual tumor's m6A modification pattern will help to guide immunotherapy strategies that shows more therapeutic effects.