Case Control Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 6, 2022; 10(22): 7686-7697
Published online Aug 6, 2022. doi: 10.12998/wjcc.v10.i22.7686
Comprehensive proteomic signature and identification of CDKN2A as a promising prognostic biomarker and therapeutic target of colorectal cancer
Qian-Qian Wang, Yuan-Chen Zhou, Yu-Jia Zhou Ge, Geng Qin, Teng-Fei Yin, Dong-Yan Zhao, Chang Tan, Shu-Kun Yao
Qian-Qian Wang, Yuan-Chen Zhou, Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 10029, China
Yu-Jia Zhou Ge, Dong-Yan Zhao, Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
Geng Qin, Shu-Kun Yao, Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
Teng-Fei Yin, Chang Tan, Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
Author contributions: Wang QQ performed the study, analyzed the data, and drafted the manuscript; Zhou YC and Zhou Ge JY collected samples from subjects; Qin G provided guidance on experimental procedures; Yin TF, Zhao DY, and Tan C collected the clinical data; Yao SK supervised the study performance, revised the manuscript, and obtained the funding; and All authors read and approved the final manuscript.
Supported by National Key Development Plan for Precision Medicine Research, No. 2017YFC0910002.
Institutional review board statement: This study was approved by the Ethics Committee of China-Japan Friendship Hospital (No. 2018-116-K85).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement, and the manuscript was prepared and revised according to the STROBE Statement.
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: Shu-Kun Yao, MD, PhD, Professor, Department of Gastroenterology, China-Japan Friendship Hospital, No. 2 Yinghua East Road, Chaoyang District, Beijing 100029, China. shukunyao@126.com
Received: March 17, 2022
Peer-review started: March 17, 2022
First decision: May 12, 2022
Revised: May 19, 2022
Accepted: June 22, 2022
Article in press: June 22, 2022
Published online: August 6, 2022
ARTICLE HIGHLIGHTS
Research background

Colorectal cancer (CRC) has become the second leading cause of cancer-related deaths worldwide; however, its specific pathogenic mechanism has not been elucidated until now. Exploring the proteomic features of CRC, mining protein prognostic biomarkers and identifying precise therapeutic targets are important for improving the prognosis of CRC patients.

Research motivation

Despite improvements in diagnosis and treatment, the overall survival of CRC patients is still not very satisfactory. In particular, the 5-year survival rate of patients with advanced CRC remains less than 20%. Therefore, there is an urgent need for the clinical discovery of novel biomarkers and therapeutic targets. With the development of proteomic technology, proteins are considered potential biomarkers and precision therapy targets in CRC.

Research objectives

To comprehensively characterize the proteomic features and identify novel prognostic biomarkers and precise therapeutic targets of CRC.

Research methods

The differentially expressed proteins (DEPs) were obtained by performing liquid chromatography–mass spectrometry detection of clinical samples, including colorectal cancer tissues and paired paracancerous tissues. Through further bioinformatic analysis, immunohistochemical (IHC) verification, and the correlation between DEPs and overall survival, protein prognostic biomarkers and therapeutic targets for CRC were identified.

Research results

The authors first provide a comprehensive characterization of the proteomic signature of CRC. Compared with normal tissues, 1115 proteins were upregulated and 705 proteins downregulated in CRC based on a P adj < 0.05 and |log2FC| > 2 criteria, and the DEPs were involved in a variety of different molecular functions and signal transduction pathways. In addition, through IHC verification and survival analysis, we found that high expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) protein was significantly correlated with poor prognosis in CRC. This demonstrated that CDKN2A could be used as a prognostic biomarker and a target for precision therapy in CRC.

Research conclusions

The proteomic signature of CRC has been comprehensively characterized, and CDKN2A has strong potential as a prognostic biomarker and a target for precision therapy in CRC.

Research perspectives

Novel protein prognostic biomarkers and precise therapeutic targets provide new opportunities to improve the prognosis of CRC patients.