Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2020; 26(2): 184-198
Published online Jan 14, 2020. doi: 10.3748/wjg.v26.i2.184
Impact of GFRA1 gene reactivation by DNA demethylation on prognosis of patients with metastatic colon cancer
Wan-Ru Ma, Peng Xu, Zhao-Jun Liu, Jing Zhou, Lian-Kun Gu, Jun Zhang, Da-Jun Deng
Wan-Ru Ma, Zhao-Jun Liu, Jing Zhou, Lian-Kun Gu, Da-Jun Deng, Key Laboratory of Carcinogenesis and Translational Research (MOE/Beijing), Division of Etiology, Peking University Cancer Hospital and Institute, Beijing 100143, China
Peng Xu, Jun Zhang, Shihezi University School of Medicine, Shihezi 832000, Xinjiang Uygur Autonomous Region, China
Peng Xu, Morphological Center of Basic Medical School of Xinjiang Medical University, Urumqi 830011, Xinjiang Uygur Autonomous Region, China
Author contributions: Deng DJ and Zhang J designed the research; Ma WR, Xu P, Zhou J, and Gu LK performed the research; Ma WR and Liu ZJ analyzed the data; Ma WR, Xu P, Zhang J, and Deng DJ wrote the paper. Ma WR and Xu P contributed equally to this work. Zhang J is an equal corresponding author.
Supported by the National Natural Science Foundation of China A3 Foresight Program, No. 31261140372; Beijing Science and Technology Commission, No. Z151100001615022; and the Science Foundation of Peking University Cancer Hospital, No. 2017-25.
Institutional review board statement: This study was reviewed and approved by The Institutional Review Board of the Peking University Cancer Hospital and Institute.
Institutional review board statement: This study was reviewed and approved by The Institutional Review Board of the Peking University Cancer Hospital and Institute.
Informed consent statement: The patients were not required to give informed consent to the study because the analysis used anonymous data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The data and materials of the study are available from the corresponding author upon reasonable request.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Da-Jun Deng, MD, Professor, Laboratory of Carcinogenesis and Translational Research (MOE/Beijing), Division of Etiology, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142, China. dengdajun@bjmu.edu.cn
Received: October 8, 2019
Peer-review started: October 8, 2019
First decision: November 11, 2019
Revised: December 14, 2019
Accepted: December 21, 2019
Article in press: December 21, 2019
Published online: January 14, 2020
Processing time: 97 Days and 8.2 Hours
Core Tip

Core tip: GFRA1 reactivation by DNA demethylation is a frequent event in colon cancer (CC) development and that the high level of GFRA1 demethylation in CC tissues is correlated with high metastasis risk of CC and shorter overall survival of patients, especially patients with metastatic CC. We find that GFRA1 overexpression enhances the proliferation and growth of CC cells in vitro and in vivo, probably by activation of the GFRA1-GDNF downstream pathway. These data indicate that reactivation of GFRA1 by DNA demethylation is an important prognosis factor for CC and the cancer-related cell membrane protein GFRA1 may be a therapeutic target for CC patients.