Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2024; 16(7): 2971-2987
Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.2971
Comprehensive serum proteomics profiles and potential protein biomarkers for the early detection of advanced adenoma and colorectal cancer
Chang Tan, Geng Qin, Qian-Qian Wang, Kai-Min Li, Yuan-Chen Zhou, Shu-Kun Yao
Chang Tan, Qian-Qian Wang, Yuan-Chen Zhou, Shu-Kun Yao, Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
Geng Qin, Shu-Kun Yao, Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
Kai-Min Li, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
Author contributions: Tan C conceived the study, collected the samples, prepared the original draft, and reviewed this manuscript; Wang QQ, Li KM and Zhou YC critically participated in the data analysis and manuscript revision. Qin G provided guidance on the study design; Yao SK supervised the study, revised the manuscript, and obtained funding; 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 conflicts of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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, Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, No. 2 Yinghua East Road, Chaoyang District, Beijing 100029, China. shukunyao@126.com
Received: November 10, 2023
Revised: March 8, 2024
Accepted: May 15, 2024
Published online: July 15, 2024
Processing time: 244 Days and 23.4 Hours
Abstract
BACKGROUND

The majority of colorectal cancer (CRC) cases develop from precursor advanced adenoma (AA). With the development of proteomics technologies, blood protein biomarkers have potential applications in the early screening of AA and CRC in the general population.

AIM

To identify serum protein biomarkers for the early screening of AA and CRC.

METHODS

We collected 43 serum samples from 8 normal controls (NCs), 19 AA patients and 16 CRC patients at China-Japan Friendship Hospital. Quantitative proteomic analysis was performed using liquid chromatography–mass spectrometry/mass spectrometry and data independent acquisition, and differentially expressed proteins (DEPs) with P-values < 0.05 and absolute fold changes > 1.5 were screened out, followed by bioinformatics analysis. Prognosis was further analyzed based on public databases, and proteins expression in tissues were validated by immunohistochemistry.

RESULTS

A total of 2132 proteins and 17365 peptides were identified in the serum samples. There were 459 upregulated proteins and 118 downregulated proteins in the NC vs AA group, 289 and 180 in the NC vs CRC group, and 52 and 248 in the AA vs CRC group, respectively. Bioinformatic analysis revealed that these DEPs had different functions and participated in extensive signaling pathways. We also identified DIAPH1, VASP, RAB11B, LBP, SAR1A, TUBGCP5, and DOK3 as important proteins for the progression of AA and CRC. Furthermore, VASP (P < 0.01), LBP (P = 0.01), TUBGCP5 (P < 0.01), and DOK3 (P < 0.01) were associated with a poor prognosis. In addition, we propose that LBP and VASP may be more promising protein biomarkers for the early screening of colorectal tumors.

CONCLUSION

Our study elucidated the serum proteomic profiles of AA and CRC patients, and the identified proteins, such as LBP and VASP, may contribute to the early detection of AA and CRC.

Keywords: Serum proteomics, Advanced adenoma, Colorectal cancer, Protein biomarker, Early screening

Core Tip: In this study, serum proteomics analysis of advanced adenoma (AA) and colorectal cancer (CRC) was comprehensively performed using liquid chromatography-mass spectrometry/mass spectrometry and data independent acquisition methods, screening for a variety of differentially expressed proteins. Among them, we identified DIAPH1, VASP, RAB11B, LBP, SAR1A, TUBGCP5, and DOK3 as important proteins for the progression of AA and CRC. Furthermore, LBP, VASP, TUBGCP5, and DOK3 were associated with a poor prognosis. In addition, we proposed that LBP and VASP may be more promising protein biomarkers for the early screening of colorectal tumors.