Copyright
©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients
Huang Chen, Rui-Ying Jiang, Zhan Hua, Xiao-Wei Wang, Xiao-Li Shi, Ye Wang, Qian-Qian Feng, Jie Luo, Wu Ning, Yan-Fen Shi, Da-Kui Zhang, Bei Wang, Jian-Zheng Jie, Ding-Rong Zhong
Huang Chen, Rui-Ying Jiang, Xiao-Wei Wang, Ye Wang, Qian-Qian Feng, Jie Luo, Yan-Fen Shi, Bei Wang, Ding-Rong Zhong, Department of Pathology, China-Japan Friendship Hospital, Beijing 100029, China
Zhan Hua, Wu Ning, Da-Kui Zhang, Jian-Zheng Jie, Department of Gastrointestinal Surgery, China-Japan Friendship Hospital, Beijing 100029, China
Xiao-Li Shi, Department of Scientific Research, Geneis, Beijing 100012, China
Author contributions: Jie JZ and Zhong DR conceived and coordinated the research; Chen H, Jiang RY, Wang Y, Feng QQ, Luo J, and Ning W collected data from patients; Chen H, Hua Z, and Wang XW analyzed data and wrote the manuscript; Shi XL, Ning W, Shi YF, Zhang DK, and Wang B revised the manuscript; and all authors read and approved the final version of the manuscript.
Supported by National High Level Hospital Clinical Research Funding, No. 2023-NHLHCRF-YYPPLC-TJ-03.
Institutional review board statement: This study was conducted in accordance with the ethical guidelines and regulations approved by the Ethics Committee of China-Japan Friendship Hospital (Approval No. QX2021-001-01).
Conflict-of-interest statement: Xiao-Li Shi is currently employed by Geneis Beijing Co. Ltd. The authors declare that this research was conducted in the absence of potential conflicts of interest.
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: Ding-Rong Zhong, MD, Chief Doctor, Department of Pathology, China-Japan Friendship Hospital, No. 2 Yinghuayuan, East Street, Chaoyang District, Beijing 100029, China. 748803069@qq.com
Received: December 4, 2023
Revised: February 23, 2024
Accepted: April 12, 2024
Published online: June 15, 2024
Processing time: 193 Days and 17 Hours
BACKGROUND
RAS, BRAF, and mismatch repair (MMR)/microsatellite instability (MSI) are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer (CRC). However, their characteristics and influencing factors in Chinese patients have not been thoroughly described.
AIM
To analyze the clinicopathological features of KRAS, NRAS, BRAF, and PIK3CA mutations and the DNA MMR status in CRC.
METHODS
We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital. MMR proteins were tested using immunohistochemical analysis, and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction. Microsatellite status was determined using an MSI detection kit. Statistical analyses were conducted using SPSS software and logistic regression.
RESULTS
The KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 44.6%, 3.4%, 3.7%, and 3.9% of CRC patients, respectively. KRAS mutations were more likely to occur in patients with moderate-to-high differentiation. BRAF mutations were more likely to occur in patients with right-sided CRC, poorly differentiated, or no perineural invasion. Deficient MMR (dMMR) was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas. KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 29.6%, 1.1%, 8.1%, and 22.3% of patients with dMMR, respectively. The dMMR was more likely to occur in patients with a family history of CRC, aged < 50 years, right-sided CRC, poorly differentiated histology, no perineural invasion, and with carcinoma in situ, stage I, or stage II tumors.
CONCLUSION
This study analyzed the molecular profiles of KRAS, NRAS, BRAF, PIK3CA, and MMR/MSI in CRC, identifying key influencing factors, with implications for clinical management of CRC.
Core Tip: This study presents a comprehensive analysis of KRAS, NRAS, BRAF, PIK3CA mutations, and mismatch repair (MMR)/microsatellite instability status in 2271 Chinese patients with colorectal cancer (CRC). Key findings include mutation frequencies, their association with clinicopathological characteristics, and the influence of MMR deficiency. These findings have significant implications for the clinical management of CRC, providing a foundation for personalized therapy and precision medicine in CRC.
