N6-Methyladenosine (m6A) is an
RNA modification that interacts with numerous coding and non-coding RNAs and plays important roles in the development of
cancers. Nonetheless, the clinical impacts of
m6A interactive genes on these
cancers largely remain unclear since most studies focus only on a single
cancer type. We comprehensively evaluated
m6A modification patterns, including 23
m6A regulators and 83 interactive coding and non-coding RNAs among 9,804 pan-
cancer samples. We used clustering analysis to identify
m6A subtypes and constructed the
m6A signature based on an unsupervised approach. We used the signatures to identify potential
m6A modification targets across the genome. The prognostic value of one target was further validated in 3,444 samples from six external datasets. We developed three distinct
m6A modification subtypes with different tumor microenvironment cell infiltration degrees: immunological, intermediate, and
tumor proliferative. They were significantly associated with overall survival in 24 of 27
cancer types. Our constructed individual-level
m6A signature was associated with survival,
tumor mutation burden, and classical pathways. With the signature, we identified 114 novel genes as potential
m6A targets. The gene shared most commonly between
cancer types, BCL9L, is an oncogene and interacts with
m6A patterns in the Wnt signaling pathway. In conclusion,
m6A regulators and their interactive genes impact the outcome of various
cancers. Evaluating the
m6A subtype and the signature of individual
tumors may inform the design of adjuvant treatments.