Role of METTL6 in gastric cancer: diagnostic, prognostic, and functional implications

Background Gastric cancer (GC) remains among the most common and lethal malignancies worldwide. The identification of novel biomarkers is critical for improving prognostic evaluation and informing therapeutic decision-making. Methyltransferase-like 6 (METTL6), a transfer RNA methyltransferase implicated in cell division, has a poorly defined biological role and mechanism in GC. Methods METTL6 expression was systematically investigated using experimental techniques and bioinformatic analyses. Comprehensive clinical and pathological data were collected to stratify patients with GC for comparative evaluation. Kaplan–Meier survival analysis and Cox proportional hazards regression models were applied to determine the prognostic significance of METTL6 expression. In parallel, immune cell infiltration associated with METTL6 expression was analyzed using data from The Cancer Genome Atlas, and the prognostic impact of METTL6 was further assessed within immune infiltration–defined subgroups. METTL6 knockdown was achieved through lentiviral transduction, and its biological effects were examined both in vitro and in vivo using colony formation, wound healing, Transwell migration and invasion assays, and xenograft mouse models. Results METTL6 was markedly overexpressed in GC cell lines. Elevated METTL6 expression was significantly associated with sex, clinical stage, histological type, histological grade, and poorer overall survival. In addition, METTL6 expression demonstrated a strong correlation with immune cell infiltration. Functional experiments showed that METTL6 knockdown significantly inhibited colony formation, wound closure, and tumor cell migration and invasion in vitro . Consistently, METTL6 silencing substantially reduced tumor volume and tumor weight in xenograft-bearing mice. Conclusion METTL6 overexpression is closely associated with an unfavorable prognosis in GC and may represent a valuable prognostic biomarker. Furthermore, METTL6 warrants further investigation as a potential therapeutic target.