Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2016; 22(18): 4515-4528
Published online May 14, 2016. doi: 10.3748/wjg.v22.i18.4515
Dissecting characteristics and dynamics of differentially expressed proteins during multistage carcinogenesis of human colorectal cancer
Fang Peng, Ying Huang, Mao-Yu Li, Guo-Qing Li, Hui-Chao Huang, Rui Guan, Zhu-Chu Chen, Song-Ping Liang, Yong-Heng Chen
Fang Peng, Song-Ping Liang, Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan Province, China
Fang Peng, Ying Huang, Mao-Yu Li, Guo-Qing Li, Hui-Chao Huang, Rui Guan, Zhu-Chu Chen, Yong-Heng Chen, Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, XiangYa Hospital, Central South University, Changsha 410008, Hunan Province, China
Ying Huang, Maternal and Child Health Hospital of Hunan Province, Changsha 410008, Hunan Province, China
Guo-Qing Li, Department of Biology, School of Pharmacy and Life Science, University of South China, Hengyang 421001, Hunan Province, China
Rui Guan, Experimental Medicine Center, Hunan Cancer Hospital, Changsha 410013, Hunan Province, China
Zhu-Chu Chen, Yong-Heng Chen, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510000, Guangdong Province, China
Author contributions: Peng F and Huang Y contributed equally to this work; Liang SP is co-corresponding author of this article; Peng F, Huang Y, Chen ZC, Liang SP and Chen YH designed the research; Peng F, Huang Y, Li MY and Li GQ performed the research; Li MY, Li GQ, Huang HC and Guan R analyzed the data; Peng F, Li MY, Huang HC, Chen ZC, Liang SP and Chen YH wrote the paper; all authors approved the final version of the manuscript.
Supported by the National “973” Project of China, No. 2011CB910704; and National Natural Science Foundation of China, No. 81372904, No. 81570537 and No. 81272971.
Institutional review board statement: The study was reviewed and approved by the XiangYa Hospital Institutional Review Board.
Conflict-of-interest statement: No conflict of interest.
Data sharing statement: Technical appendix, and dataset available from the corresponding author at email yonghengchen@gmail.com.
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/
Correspondence to: Yong-Heng Chen, MD, PhD, Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, XiangYa Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China. yonghengchen@gmail.com
Telephone: +86-731-84327608 Fax: +86-731-84327608
Received: December 7, 2015
Peer-review started: December 7, 2015
First decision: December 30, 2015
Revised: February 13, 2016
Accepted: March 18, 2016
Article in press: March 18, 2016
Published online: May 14, 2016
Processing time: 149 Days and 0.6 Hours
Abstract

AIM: To discover novel biomarkers for early diagnosis, prognosis or treatment of human colorectal cancer.

METHODS: iTRAQ 2D LC-MS/MS analysis was used to identify differentially expressed proteins (DEPs) in the human colonic epithelial carcinogenic process using laser capture microdissection-purified colonic epithelial cells from normal colon, adenoma, carcinoma in situ and invasive carcinoma tissues.

RESULTS: A total of 326 DEPs were identified, and four DEPs (DMBT1, S100A9, Galectin-10, and S100A8) with progressive alteration in the carcinogenic process were further validated by immunohistochemistry. The DEPs were involved in multiple biological processes including cell cycle, cell adhesion, translation, mRNA processing, and protein synthesis. Some of the DEPs involved in cellular process such as “translation” and “mRNA splicing” were progressively up-regulated, while some DEPs involved in other processes such as “metabolism” and “cell response to stress” was progressively down-regulated. Other proteins with up- or down-regulation at certain stages of carcinogenesis may play various roles at different stages of the colorectal carcinogenic process.

CONCLUSION: These findings give insights into our understanding of the mechanisms of colorectal carcinogenesis and provide clues for further investigation of carcinogenesis and identification of biomarkers.

Keywords: Colorectal Cancer; Proteome; Biomarker; Carcinogenesis

Core tip: In this study, we used iTRAQ 2D LC-MS/MS analysis to identify differentially expressed proteins (DEPs) in the human colonic epithelial carcinogenic process using laser capture microdissection-purified colonic epithelial cells from normal colon, adenoma, carcinoma in situ and invasive carcinoma tissues. A total of 326 DEPs were identified. Four DEPs (DMBT1, S100A9, Galectin-10, and S100A8) with progressive alteration in the carcinogenic process were further validated using immunohistochemistry. The DEPs were involved in multiple biological processes including cell cycle, cell adhesion, translation, mRNA processing, and protein synthesis. These findings give insights into our understanding of the mechanisms of colorectal carcinogenesis and provide clues for further investigation of carcinogenesis and identification of biomarkers.