Lu YW, Ding ZL, Mao R, Zhao GG, He YQ, Li XL, Liu J. Early results of the integrative epigenomic-transcriptomic landscape of colorectal adenoma and cancer. World J Gastrointest Oncol 2024; 16(2): 414-435 [PMID: PMC10900154 DOI: 10.4251/wjgo.v16.i2.414]
Corresponding Author of This Article
Jiang Liu, PhD, Senior Scientist, Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming 650032, Yunnan Province, China. liujiang6787@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
You-Wang Lu, Department of Dermatology and Venereology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
Zhao-Li Ding, Kunming Biological Diversity Regional Center of Large Apparatus and Equipments, Public Technical Service Center, Kunming Institute of Zoology, Kunming 650223, Yunnan Province, China
Rui Mao, School of Stomatology, Kunming Medical University, Kunming 650500, Yunnan Province, China
Gui-Gang Zhao, Yu-Qi He, Xiao-Lu Li, Genome Center of Biodiversity, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, Yunnan Province, China
Jiang Liu, Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
Co-first authors: You-Wang Lu and Zhao-Li Ding.
Author contributions: Liu J contributed to the conceptualization of this study; Ding ZL and Zhao GG involved in the investigation of this article; Lu YW and Mao R took part in the formal analysis of this manuscript; Lu YW and Liu J participated in the writing - original draft of this manuscript; He YQ and Li XL contributed to the writing - review & editing of this article.
Supported bythe National Natural Science Foundation of China, No. 81960504; the “Xingdian Talents” Support Project of Yunnan Province, No. RLQB20200002; the Medical Discipline Reserve Talents of Yunnan Province, No. H-2018015; the Applied Basic Research Projects-Union Foundation of Kunming Medical University, No. 2017FE467(-132); and the Talent Introduction Project of Hubei Polytechnic University, No. 21xjz34R.
Institutional review board statement: This study was approved by the Ethics Committee of the First Affiliated Hospital of Kunming Medical University.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All the raw data for WGBS and RNA-Seq have been deposited in the SRA database (BioProject Number:PRJNA996378). Technical appendix, and statistical code available from the corresponding author at liujiang6787@163.com.
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: Jiang Liu, PhD, Senior Scientist, Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming 650032, Yunnan Province, China. liujiang6787@163.com
Received: August 17, 2023 Peer-review started: August 17, 2023 First decision: November 6, 2023 Revised: November 24, 2023 Accepted: December 22, 2023 Article in press: December 22, 2023 Published online: February 15, 2024 Processing time: 169 Days and 7.3 Hours
Abstract
BACKGROUND
Aberrant methylation is common during the initiation and progression of colorectal cancer (CRC), and detecting these changes that occur during early adenoma (ADE) formation and CRC progression has clinical value.
AIM
To identify potential DNA methylation markers specific to ADE and CRC.
METHODS
Here, we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.
RESULTS
Comparing 22 CRC and 25 ADE samples, global methylation was higher in the former, but both showed similar methylation patterns regarding differentially methylated gene positions, chromatin signatures, and repeated elements. High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC. Combined with RNA-seq gene expression data, we identified 14 methylation-regulated differentially expressed genes, of which only AGTR1 and NECAB1 methylation had prognostic significance.
CONCLUSION
Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC, suggesting prognostic biomarkers for CRC.
Core Tip: Despite enhanced global methylation in colorectal cancer (CRC), both adenoma and CRC share similar methylation patterns. High-grade CRC tends to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC. The integration of gene expression data identified 14 methylation-regulated differentially expressed genes, with AGTR1 and NECAB1 methylation being prognostically significant.
