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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Anoctamin 5 regulates the cell cycle and affects prognosis in gastric cancer
Tomoyuki Fukami, Atsushi Shiozaki, Toshiyuki Kosuga, Michihiro Kudou, Hiroki Shimizu, Takuma Ohashi, Tomohiro Arita, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Mitsuo Kishimoto, Yukiko Morinaga, Eiichi Konishi, Eigo Otsuji
Tomoyuki Fukami, Atsushi Shiozaki, Toshiyuki Kosuga, Michihiro Kudou, Hiroki Shimizu, Takuma Ohashi, Tomohiro Arita, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
Mitsuo Kishimoto, Department of Pathology, Kyoto City Hospital, Kyoto 604-8845, Japan
Yukiko Morinaga, Eiichi Konishi, Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
Author contributions: Fukami T and Shiozaki A contributed equally to this work; All authors read and approved the final manuscript and agreed to be accountable for all aspects of the report.
Supported by Japan Society for the Promotion of Science, No. 21K08689, No. 21K16456, No. 20K09016, No. 20K09084, No. 19K09202 and No. 19K09182.
Institutional review board statement: The study was reviewed and approved by the Kyoto Prefectural University of Medicine Institutional Review Board, No. ERB-C-1195.
Informed consent statement: Informed consent to be included in the study, or the equivalent, was obtained from all patients.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at shiozaki@koto.kpu-m.ac.jp. Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Atsushi Shiozaki, MD, PhD, Assistant Professor, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. shiozaki@koto.kpu-m.ac.jp
Received: February 28, 2022
Peer-review started: February 28, 2022
First decision: May 9, 2022
Revised: June 10, 2022
Accepted: July 27, 2022
Article in press: July 27, 2022
Published online: August 28, 2022
ARTICLE HIGHLIGHTS
Research background
Anoctamin 5 (ANO5) is a member of a family of calcium-activated chloride channels containing 10 members, also known as transmembrane proteins, and has been reported to be associated with various cancers.
Research motivation
The role of ANO5 in gastric cancer (GC) remains poorly understood. In the present study, we analyzed the relationship between ANO5 expression and tumor progression in GC.
Research objectives
The objectives of the present study were to investigate whether ANO5 contributes to the regulation of cancer growth and to clarify its clinicopathological significance in GC.
Research methods
Knockdown experiments were performed by transfecting human GC cell lines with ANO5 small interfering RNA. Gene expression was then assessed using microarray analysis. Samples from 195 patients with GC were subjected to immunohistochemistry for ANO5, and its relationship with clinicopathological factors and prognosis were examined.
Research results
ANO5 knockdown suppressed the proliferation, migration, and invasion of cells and enhanced apoptosis. Cell cycle analysis showed that ANO5 knockdown suppressed the progression of G1-S phase. The results of microarray analysis showed up- or downregulated expression of genes related to “Cell Cycle: G1/S Checkpoint Regulation” in ANO5 knockdown NUGC4 cells. Survival analysis showed significantly poorer 5-year survival in the ANO5 high expression group (high vs low; 73.9 vs 89.6%, P = 0.0104). Immunohistochemistry multivariate analysis identified the high expression of ANO5 as an independent prognostic factor for 5-year survival in GC patients (P = 0.0457).
Research conclusions
ANO5 plays a significant role in cell cycle progression in human GC cells. The results of the immunohistochemistry analysis suggest that high ANO5 expression levels are a poor prognostic factor in patients with GC.
Research perspectives
The present study may contribute to the identification of ANO5 as a key mediator in tumor progression, with it ultimately being a promising prognostic biomarker or a novel therapeutic target of GC.
