Classification and immune invasion analysis of breast cancer based on m6A genes.

BACKGROUND

Breast cancer (BRCA) shows genetic, epigenetic, and phenotypic diversity. Methylation of N6-methyladenosine (m6A) affects the occurrence, development, and therapeutic efficacy of BRCA. However, the characteristics and prognostic value of m6A in BRCA remain unclear. We aimed to classify and construct a scoring system for the m6A regulatory gene in BRCA, and to explore its potential mechanisms.

METHODS

In this study, we selected 23 m6A regulatory genes and analyzed their genetic variation in BRCA, including copy number variation (CNV) data, expression differences, mutations, gene types, and correlations between genes. Survival curves were drawn by the Kaplan-Meier method, and a log-rank P<0.05 was considered statistically significant. The partitioning around medoids (PAM) algorithm was used for molecular subtype analysis of m6A, single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to quantify the relative infiltration levels of various immune cell subgroups, and a scoring system was built based on principal component analysis (PCA).

RESULTS

In BRCA, m6A regulatory gene mutation frequency is not high, while that of CNV mutation is high, which is related to gene expression and closely related to prognosis. In this study, we identified 3 different m6A subtypes, which are closely related to the level of immune cell infiltration. We further constructed an m6A score system, in which lower scores were correlated with low tumor mutation burden (TMB), later clinical staging, programmed cell death 1 ligand 1 (PD-L1) expression, and triple-negative breast cancer (TNBC).

CONCLUSIONS

This study highlights the diversity and complexity of the role of m6A in BRCA. The classification of BRCA based on the m6A regulatory gene can help us understand the characteristics of BRCA and help develop individualized immunotherapy regimens.