Characterization of the mA regulator-mediated methylation modification patterns in oral squamous cell carcinoma.

N-methyladenosine (mA) 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 mA modification. In addition, the role of mA modification in shaping immune cell infiltration in OSCC has yet to be clarified. This study was designed to assess mA modification dynamics in OSCC and to understand how such modifications influence clinical immunotherapeutic treatment outcomes. mA modification patterns linked with 23 mA regulators were analyzed in 437 OSCC patients from TCGA and GEO cohorts. These patterns were then quantified through mA score based on algorithms derived from a principal component analysis (PCA) approach. The mA modification patterns of OSCC samples were grouped into two clusters based on the mA 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 mA regulator expression exhibited poorer overall survival (OS), whereas patients with high mA scores survived for longer (p < 0.001). The overall mortality rates in the groups of patients with low and high mA scores were 55% and 40%, respectively, and the mA score distributions in clusters of patients grouped by mA modification patterns and gene expression further supported the link between a high mA score and better prognostic outcomes. Immunophenoscore (IPS) values for patients in different mA 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-mA score group relative to the low-mA score group. mA modification patterns are relevant to heterogeneity in OSCC. Detailed analyses of mA 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.