Prognostic significance of N6-methyladenosine-modified related chemotransferase METTL3 in gastric carcinoma: Evidence from meta-analysis.

Abstract

Background: N6-methyladenosine (m⁶A) methylation is known as the research hotspot for tumor epimodification, and its associated methyltransferase-like3 (METTL3) is significantly differentially expressed in gastric carcinoma, but its clinical value has not been summarized. This meta-analysis aimed to evaluate the prognostic significance of METTL3 in gastric carcinoma.

Material and methods: Databases, including PubMed, EMBASE (Ovid platform), Science Direct, Scopus, MEDLINE, Google Scholar, Web of Science, and Cochrane Library, were used to identify relevant eligible studies. The endpoints included overall survival, progression-free survival, recurrence-free survival, post-progression survival, and disease-free survival. Hazard ratios (HR) with 95% confidence intervals (CI) were used to correlate METTL3 expression with prognosis. Subgroup and sensitivity analyses were performed.

Results: Seven eligible studies involving 3034 gastric carcinoma patients were recruited for this meta-analysis. The analysis showed that high METTL3 expression was associated with significantly poorer overall survival (HR  =  2.37, 95% CI 1.66-3.39, P < 0.01) and unfavorable disease-free survival (HR  =  2.58, 95% CI 1.97-3.38, P  < 0.01), as did unfavorable progression-free survival (HR  =  1.48, 95% CI 1.19-1.84, P  < 0.01)/recurrence-free survival (HR  =  2.62, 95% CI 1.93-5.62, P  < 0.01)/post-progression survival (HR  =  1.53, 95% CI 1.22-1.91, P  < 0.01). Subgroup analysis found that high METTL3 expression was associated with worse overall survival in patients with Chinese (HR  =  2.21, 95% CI 1.48-3.29, P  < 0.01), in studies with sample source from formalin-fixed, paraffin-embedded tissues (HR  =  2.66, 95% CI 1.79-3.94, P  < 0.01), and the reported directly from articles group (HR  =  2.42, 95% CI 1.66-3.53, P  < 0.01). The subgroup analysis that was performed based on sample size, detected method, and follow-up showed the same results.

Conclusions: High expression of METTL3 predicts poor prognosis in gastric carcinoma, indicating promise for METTL3 as a prognostic biomarker.Systematic review registration: https://www.crd.york.ac.uk/prospero, ID = CRD42023408519.