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Published December 23, 2022 | Published
Journal Article Open

Prognostic potential of METTL3 expression in patients with gastric cancer

Abstract

Methyltransferase‑like 3 (METTL3) is a crucial component of the m6A methyltransferase complex, which serves pivotal roles in tumor progression. The present study investigated the prognostic significance of METTL3 expression in gastric cancer (GC). The expression levels of METTL3 were assessed by immunohistochemistry in formalin‑fixed paraffin‑embedded (FFPE) tissue specimens from 158 patients with GC. Propensity score matching (PSM) analysis was performed to clarify its prognostic potential. METTL3 gene expression was also investigated in fresh frozen specimens from another independent cohort of 57 patients with GC to establish its clinical relevance. Knockdown of METTL3 by small interfering RNA transfection was performed to evaluate its function in vitro. METTL3 expression was significantly higher in cancerous tissues compared with in corresponding normal mucosa (P<0.0001), and high METTL3 expression was an independent prognostic factor for overall and disease‑free survival in the FFPE cohort of patients with GC. PSM analysis revealed that elevated METTL3 expression was significantly associated with poor survival outcomes, which was subsequently validated in another cohort of fresh frozen specimens. Knockdown of METTL3 inhibited proliferation, invasion, migration and anoikis resistance in GC cells. In conclusion, METTL3 expression may be used as a clinically feasible prognostic marker and could serve as a potential therapeutic target in patients with GC.

Additional Information

This work was supported in part by Grants-in-Aid for Scientific Research (grant nos. 18K08566, 18K08700, 18K08674, 18K08591 and 20K09004) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. Availability of data and materials. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Authors' contributions. YO, YT, MO and KN conceived and designed the study. TI, HI, TK, TS, MK, HY, HF, TY and MO provided the samples. YO, YT, CY, MR, TI, HI, TK, TS, MK, TY, and IM acquired the data. YO, YT, AG, MR, HY, HF, IM, MO and KN analyzed and interpretated the data. YO and YT performed the statistical analysis. YO, YT, AG, MO and KN drafted the manuscript. YO and YT confirm the authenticity of raw data. All authors read and approved the final manuscript. Ethics approval and consent to participate: The present study was approved by the Institutional Review Board of Mie University (approval no. H2019-197). The requirement for informed consent was waived, and an information disclosure statement was uploaded onto the homepage of our hospital website for opt-out. Patient consent for publication: Not applicable. All authors declare that they have no competing interests.

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Additional details

Created:
August 22, 2023
Modified:
October 24, 2023