Characterization of the m(6)A regulator-mediated methylation modification patterns in oral squamous cell carcinoma

N(6)-methyladenosine (m(6)A) is a form of posttranscriptional modification that plays important roles in cancer including oral squamous cell carcinoma (OSCC). Most studies to date have focused on a limited number of regulators and oncogenic pathways, thus failing to provide comprehensive insight into the dynamic effects of m(6)A modification. In addition, the role of m(6)A modification in shaping immune cell infiltration in OSCC has yet to be clarified. This study was designed to assess m(6)A modification dynamics in OSCC and to understand how such modifications influence clinical immunotherapeutic treatment outcomes. m(6)A modification patterns linked with 23 m(6)A regulators were analyzed in 437 OSCC patients from TCGA and GEO cohorts. These patterns were then quantified through m(6)A score based on algorithms derived from a principal component analysis (PCA) approach. The m(6)A modification patterns of OSCC samples were grouped into two clusters based on the m(6)A regulators expression, and immune cell infiltration was linked with the 5-year survival outcomes of patients in these clusters. 1575 genes associated with OSCC patient prognosis were identified and used to re-cluster these samples into two groups. Patients in clusters exhibiting higher levels of m(6)A regulator expression exhibited poorer overall survival (OS), whereas patients with high m(6)A scores survived for longer (p < 0.001). The overall mortality rates in the groups of patients with low and high m(6)A scores were 55% and 40%, respectively, and the m(6)A score distributions in clusters of patients grouped by m(6)A modification patterns and gene expression further supported the link between a high m(6)A score and better prognostic outcomes. Immunophenoscore (IPS) values for patients in different m(6)A score groups suggested that the use of PD-1-specific antibodies or CTLA-4 inhibitors alone or in combination would yield superior treatment outcomes in patients in the high-m(6)A score group relative to the low-m(6)A score group. m(6)A modification patterns are relevant to heterogeneity in OSCC. Detailed analyses of m(6)A modification patterns may thus offer novel insight regarding immune cell infiltration within the OSCC tumor microenvironment, guiding novel efforts to provide patients with more effective immunotherapeutic interventions.