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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2020; 26(2): 154-167
Published online Jan 14, 2020. doi: 10.3748/wjg.v26.i2.154
Novel methylation gene panel in adjacent normal tissues predicts poor prognosis of colorectal cancer in Taiwan
Chih-Hsiung Hsu, Cheng-Wen Hsiao, Chien-An Sun, Wen-Chih Wu, Tsan Yang, Je-Ming Hu, Chi-Hua Huang, Yu-Chan Liao, Chao-Yang Chen, Fu-Huang Lin, Yu-Ching Chou
Chih-Hsiung Hsu, Je-Ming Hu, Yu-Ching Chou, Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan
Chih-Hsiung Hsu, Teaching Office, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
Cheng-Wen Hsiao, Je-Ming Hu, Chao-Yang Chen, Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
Chien-An Sun, Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City 242, Taiwan
Chien-An Sun, Big Data Research Center, College of Medicine, Fu-Jen Catholic University, New Taipei City 242, Taiwan
Wen-Chih Wu, Chi-Hua Huang, Yu-Chan Liao, Fu-Huang Lin, Yu-Ching Chou, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan
Wen-Chih Wu, Department of Surgery, Suao and Yuanshan Branches of Taipei Veterans General Hospital, Yilan County 264, Taiwan
Tsan Yang, Department of Health Business Administration, Meiho University, Pingtung County 912, Taiwan
Je-Ming Hu, Chao-Yang Chen, Adjunct Instructor, School of Medicine, National Defense Medical Center, Taipei 114, Taiwan
Author contributions: Hsu CH and Chou YC designed the research; Hsiao CW, Sun CA, Wu WC, and Yang T performed the research; Hsiao CW, Hu JM, and Chen CY collected the data; Hsu CH, Huang CH, Liao YC, Lin FH, and Chou YC analyzed the data; Hsu CH and Chou YC wrote the paper.
Supported by the Ministry of Science and Technology, Taiwan, No. MOST 104-2314-B-016-010-MY2 and No. MOST 106-2320-B-016-018; and the Ministry of National Defense, Taiwan, No. MAB-107-075, No. MAB-108-057 and No. MAB-109-061.
Institutional review board statement: This study was approved by the TSGH Institutional Review Board (TSGHIRB approval number: 098-05-292 and 2-105-05-129).
Informed consent statement: Written informed consent was obtained from all patients before enrollment into the study to evaluate their prognosis.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised 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: Yu-Ching Chou, PhD, Associate Professor, School of Public Health, National Defense Medical Center, No. 161 Sec. 6, Minquan E. Road, Neihu District, Taipei 114, Taiwan. trishow@mail.ndmctsgh.edu.tw
Received: October 24, 2019
Peer-review started: October 24, 2019
First decision: December 5, 2019
Revised: December 14, 2019
Accepted: December 21, 2019
Article in press: December 21, 2019
Published online: January 14, 2020
ARTICLE HIGHLIGHTS
Research background
Cancer staging systems, including tumor-node-metastasis classification, facilitate reasonable adjuvant treatment and help predict the prognoses of tumors. However, part of low-risk colorectal cancer (CRC) patients experience relapse after therapeutic intervention. The prognostic factors that define these relapse-prone patients should be identified to optimize treatment selection. Recently, there were several novel prognostic biomarkers for CRC which involve epigenetic aberrant changes have been reported.
Research motivation
To determine the effect of the methylation status of a novel methylation gene panel on the relationship between the cancer stage and prognosis of CRC.
Research objectives
This study aimed to explore the relationship between the methylation status of candidate genes and prognosis of CRC.
Research methods
One hundred and twenty CRC patients from Taiwan were enrolled to evaluate the association between hypermethylation of candidate genes and prognosis. The promoter methylation status of CDKN2A, hMLH1, MGMT, CSF2, DIS3L2, and OAF genes in tumor and adjacent normal tissues was assessed using methylation-specific PCR. Associations of the number of hypermethylated genes under study and different clinical stages with time to progression (TTP) or overall survival (OS) were assessed using the Cox proportional hazards regression model. Kaplan-Meier univariate assay was performed to analyze potential prognostic factors including TTP and OS.
Research results
The ≥ 3 aberrancy methylation group showed a significantly shorter 5-year TTP than the < 3 aberrancy methylation group. There was a significant interaction between CRC prognosis and different cancer stages (local and advanced) according to the methylation status of the selected genes in both types of tissues. However, the 5-year OS of patients with CRC in the ≥ 3 aberrancy group and the < 3 aberrancy group revealed no significant differences in both types of tissues.
Research conclusions
Our data identified these novel methylation markers, particularly in the adjacent normal tissues in patients with advanced stage, and provided a basis to apply and investigate the potential of these markers to predict the prognosis of CRC.
Research perspectives
Based on our findings, these novel markers in adjacent normal tissues of patients with CRC are recommended to help in clinical decision-making. Future cohort researches are needed to validate the utility of the new set of markers and address whether the modification of treatment/management decisions based on additional prognostic information from these markers would improve the TTP and OS of patients with CRC.
