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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2022; 28(8): 825-839
Published online Feb 28, 2022. doi: 10.3748/wjg.v28.i8.825
Differential DNA methylation analysis of SUMF2, ADAMTS5, and PXDN provides novel insights into colorectal cancer prognosis prediction in Taiwan
Jing-Quan Su, Pin-Yu Lai, Pei-Hsuan Hu, Je-Ming Hu, Pi-Kai Chang, Chao-Yang Chen, Jia-Jheng Wu, Yu-Jyun Lin, Chien-An Sun, Tsan Yang, Chih-Hsiung Hsu, Hua-Ching Lin, Yu-Ching Chou
Jing-Quan Su, School of Medicine, National Defense Medical Center, Taipei 114, Taiwan
Pin-Yu Lai, Pei-Hsuan Hu, Jia-Jheng Wu, Yu-Jyun Lin, Chih-Hsiung Hsu, Yu-Ching Chou, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan
Je-Ming Hu, Pi-Kai Chang, Chao-Yang Chen, Division of Colorectal Surgery, Department of surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
Je-Ming Hu, Yu-Ching Chou, Graduate Institute of Medical Sciences, 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
Tsan Yang, Department of Health Business Administration, Meiho University, Pingtung County 912, Taiwan
Hua-Ching Lin, Division of Colorectal Surgery, Department of Surgery, Cheng-Hsin General Hospital, Taipei 112, Taiwan
Author contributions: Hsu CH, Lin HC and Chou YC contributed equally to this work; Su JQ, Hsu CH, Lin HC and Chou YC designed the research; Sun CA and Yang T performed the research; Hu JM, Chang PK and Chen CY collected the data; Su JQ, Lai PY, Hu PH, Wu JJ and Lin YJ analyzed the data; Su JQ wrote the original draft; Hsu CH, Lin HC and Chou YC wrote the review and editing; Chou YC was the project administration.
Supported by Ministry of National Defense-Medical Affairs Bureau, Taiwan, No. MND-MAB-110-109 and No. MND-MAB-D-111059; and Cheng-Hsin General Hospital, Taiwan, No. CHNDMC-111-4.
Institutional review board statement: This study was approved by the TSGH Institutional Review Board (TSGHIRB approval No. 098-05-292 and No. 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.
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: Yu-Ching Chou, PhD, 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 17, 2021
Peer-review started: October 17, 2021
First decision: December 12, 2021
Revised: December 24, 2021
Accepted: January 22, 2022
Article in press: January 22, 2022
Published online: February 28, 2022
ARTICLE HIGHLIGHTS
Research background
The tumor–node–metastasis (TNM) cancer staging system provides clinical guidelines for the classification of tumors and prediction of outcomes. However, patients within the same stage can have markedly different outcomes. For example, some patients with an early disease stage of colorectal cancer (CRC) experience relapse after surgical treatment. Prognostic factors related to relapse or progression should be considered to improve treatment selection. The combination of several novel prognostic biomarkers involving epigenetic changes may aid CRC prognosis predictions.
Research motivation
To investigate the impact of the differential DNA methylation of novel candidate genes on CRC prognosis.
Research objectives
This study focused on the association between CRC prognosis and the status and level of differential DNA methylation of candidate genes.
Research methods
In total, 208 patients with CRC were recruited to assess the relationship between the methylation status of selected genes and clinical outcomes after surgical resection. The methylation statuses of SUMF2, ADAMTS5, and PXDN in tumor tissue and tumor-free adjacent areas were evaluated through a methylation-specific polymerase chain reaction (MS-PCR), and the methylation degrees of SUMF2 and ADAMTS5 were assessed using EpiTYPER DNA methylation analysis. The relationships of gene methylation with recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) were evaluated using a Cox proportional hazards model and Kaplan–Meier survival curves.
Research results
CpG_3+CpG_7 hypermethylation of SUMF2 from tumor tissue was associated with significantly shorter PFS and OS compared with CpG_3+CpG_7 hypomethylation. CpG_2 and CpG_13 hypermethylation of ADAMTS5 from normal tissue was associated with a significantly longer RFS compared with CpG_2 and CpG_13 hypomethylation. No significant difference was noted in the association between the methylation status of PXDN in both tissue types and CRC prognosis.
Research conclusions
These results can be applied to develop useful prognostic biomarkers of CRC, especially the methylation of certain CpG islands of candidate genes. The results can add value to current cancer staging systems.
Research perspectives
Examining the differential DNA methylation of candidate genes could aid in clinical decision-making related to CRC. Further validation and investigations involving larger cohorts are required to confirm the utility of these new epigenetic biomarkers and determine whether they can be used to improve the RFS, PFS, and OS of patients with CRC.
