Okugawa Yoshinaga, Toiyama Yuji, Yin Chengzeng, Ruiya Ma, Goel Akul, Ichikawa Takashi, Imaoka Hiroki, Kitajima Takahito, Shimura Tadanobu, Kawamura Mikio, Yasuda Hiromi, Fujikawa Hiroyuki, Yokoe Takeshi, Mochiki Ikuyo, Ohi Masaki, Nakatani Kaname
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.
Oncol Lett. 2022 Dec 23;25(2):64. doi: 10.3892/ol.2022.13651. eCollection 2023 Feb.
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 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.
甲基转移酶样3（METTL3）是m6A甲基转移酶复合物的关键组成部分，在肿瘤进展中起关键作用。本研究调查了METTL3表达在胃癌（GC）中的预后意义。通过免疫组织化学对158例GC患者福尔马林固定石蜡包埋（FFPE）组织标本中的METTL3表达水平进行评估。进行倾向评分匹配（PSM）分析以阐明其预后潜力。还在另一组57例GC患者的新鲜冷冻标本中研究了METTL3基因表达，以确定其临床相关性。通过小干扰RNA转染敲低METTL3以评估其功能。与相应的正常黏膜相比，癌组织中METTL3表达明显更高（P<0.0001），并且高METTL3表达是GC患者FFPE队列总生存和无病生存的独立预后因素。PSM分析显示，METTL3表达升高与不良生存结果显著相关，随后在另一组新鲜冷冻标本中得到验证。敲低METTL3可抑制GC细胞的增殖、侵袭、迁移和失巢凋亡抗性。总之，METTL3表达可作为临床上可行的预后标志物，并可作为GC患者的潜在治疗靶点。
