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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
BACKGROUND
Patients with colorectal cancer (CRC) undergo surgery, as well as perioperative chemoradiation or adjuvant chemotherapy primarily based on the tumor–node– metastasis (TNM) cancer staging system. However, treatment responses and prognostic outcomes of patients within the same stage vary markedly. The potential use of novel biomarkers can improve prognostication and shared decision making before implementation into certain therapies.
AIM
To investigate whether SUMF2, ADAMTS5, and PXDN methylation status could be associated with CRC prognosis.
METHODS
We conducted a Taiwan region cohort study involving 208 patients with CRC recruited from Tri-Service General Hospital and applied the candidate gene approach to identify three genes involved in oncogenesis pathways. A methylation-specific polymerase chain reaction (MS-PCR) and EpiTYPER DNA methylation analysis were employed to detect methylation status and to quantify the methylation level of candidate genes in tumor tissue and adjacent normal tissue from participants. We evaluated SUMF2, ADAMTS5, and PXDN methylation as predictors of prognosis, including recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS), using a Cox regression model and Kaplan–Meier analysis.
RESULTS
We revealed various outcomes related to methylation and prognosis. Significantly shorter PFS and OS were associated with the CpG_3+CpG_7 hypermethylation of SUMF2 from tumor tissue compared with CpG_3+CpG_7 hypomethylation [hazard ratio (HR) = 2.24, 95% confidence interval (CI) = 1.03-4.85 for PFS, HR = 2.56 and 95%CI = 1.08-6.04 for OS]. By contrast, a significantly longer RFS was associated with CpG_2 and CpG_13 hypermethylation of ADAMTS5 from normal tissue compared with CpG_2 and CpG_13 hypomethylation [HR (95%CI) = 0.15 (0.03-0.71) for CpG_2 and 0.20 (0.04-0.97) for CpG_13]. The relationship between the methylation status of PXDN and the prognosis of CRC did not reach statistical significance.
CONCLUSION
Our study found that 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. These methylation-related biomarkers which have implications for CRC prognosis prediction may aid physicians in clinical decision-making.
Core Tip: Our research revealed that differential DNA methylation of candidate genes in tumor tissue and adjacent normal tissue can be used to evaluate colorectal cancer prognosis. Certain CpG sites and the methylation status of SUMF2 and ADAMTS5 were significantly associated with colorectal cancer recurrence, progression, and survival. We recommend using our findings to investigate prognostic biomarkers applicable to patients with colorectal cancer.
