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

RNA N6-Methyladenosine Modification in DNA Damage Response and Cancer Radiotherapy

“…METTL3 has been reported to have a favourable effect on tumour growth and is a risk factor for cancer prognosis in various tumour [ 66 , 67 , 68 , 69 ]. Visvanathan et al reported a higher level of M6A modification glioma stem-like cells (GSCs) and METTL3-dependent M6A modification is crucial for GSC maintenance [ 45 ].…”