m6A-related genes ALKBH5 and RBMX as prognostic and progression biomarkers in Chinese oral squamous cell carcinoma patients.

Objective: N6-methyladenosine (m6A) RNA dysregulation is crucial for cancer development. The study aimed to explore the effects of m6A modification in oral squamous cell carcinoma (OSCC) and its potential as a biomarker and therapeutic target.

Design: We first analyzed m6A-related gene expression and its impact on OSCC prognosis and progression using the TCGA database. Subsequently, a Chinese cohort of 134 samples was used for validation. Bioinformatics analysis was conducted with TCGA data, and m6A levels were measured in the validation cohort using a quantification kit. Survival analysis was performed to study the relationship between m6A-related genes and OSCC prognosis in the Chinese population. The expression of m6A-related genes was assessed by using quantitative real-time PCR, Western blot analysis, and immunohistochemistry.

Results: In the TCGA database, we found dysregulated expressions of METTL14, ALKBH5, YTHDF2, HNRNPC, LRPPRC, HNRNPA2B1, IGF2BP2, and RBMX in OSCC. Based on this, we observed significantly elevated total m6A content in OSCC tissues compared to normal controls in the validation cohort. Among the m6A candidate genes, only ALKBH5 and RBMX upregulation were found to be independent prognostic risk factors for poor OSCC survival in the Chinese population. And the inclusion of these two genes had a higher area under the curve for 3-year (0.705, 0.826), and 5-year (0.715, 0.788) overall survival compared to the model that only considered clinical parameters.

Conclusions: We found the upregulation of m6A status in OSCC, of which, ALKBH5 and RBMX may serve as promising diagnostic and prognostic biomarkers for Chinese patients with OSCC.