Prognostic potential of METTL3 expression in patients with gastric cancer

Okugawa,Yoshinaga; Okugawa,Yoshinaga; Toiyama,Yuji; Toiyama,Yuji; Yin,Chengzeng; Yin,Chengzeng; Ruiya,Ma; Ruiya,Ma; Goel,Akul; Goel,Akul; Ichikawa,Takashi; Ichikawa,Takashi; Imaoka,Hiroki; Imaoka,Hiroki; Kitajima,Takahito; Kitajima,Takahito; Shimura,Tadanobu; Shimura,Tadanobu; Kawamura,Mikio; Kawamura,Mikio; Yasuda,Hiromi; Yasuda,Hiromi; Fujikawa,Hiroyuki; Fujikawa,Hiroyuki; Yokoe,Takeshi; Yokoe,Takeshi; Mochiki,Ikuyo; Mochiki,Ikuyo; Ohi,Masaki; Ohi,Masaki; Nakatani,Kaname; Nakatani,Kaname

doi:10.3892/ol.2022.13651

Prognostic potential of METTL3 expression in patients with gastric cancer

Authors:
- Yoshinaga Okugawa
- Yuji Toiyama
- Chengzeng Yin
- Ma Ruiya
- Akul Goel
- Takashi Ichikawa
- Hiroki Imaoka
- Takahito Kitajima
- Tadanobu Shimura
- Mikio Kawamura
- Hiromi Yasuda
- Hiroyuki Fujikawa
- Takeshi Yokoe
- Ikuyo Mochiki
- Masaki Ohi
- Kaname Nakatani
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Affiliations: Department of Genome Medicine, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan, Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan, California Institute of Technology, Pasadena, CA 91125, USA
Published online on: December 23, 2022 https://doi.org/10.3892/ol.2022.13651
Article Number: 64

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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.

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