Retrospective Cohort Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2023; 29(32): 4883-4899
Published online Aug 28, 2023. doi: 10.3748/wjg.v29.i32.4883
Different oncological features of colorectal cancer codon-specific KRAS mutations: Not codon 13 but codon 12 have prognostic value
Hong-Min Ahn, Duck-Woo Kim, Hyeon Jeong Oh, Hyung Kyung Kim, Hye Seung Lee, Tae Gyun Lee, Hye-Rim Shin, In Jun Yang, Jeehye Lee, Jung Wook Suh, Heung-Kwon Oh, Sung-Bum Kang
Hong-Min Ahn, Duck-Woo Kim, Tae Gyun Lee, Hye-Rim Shin, In Jun Yang, Jeehye Lee, Jung Wook Suh, Heung-Kwon Oh, Sung-Bum Kang, Department of Surgery, Seoul National University Bundang Hospital, Seongnam 13620, South Korea
Hyeon Jeong Oh, Hyung Kyung Kim, Department of Pathology, Seoul National University Bundang Hospital, Seongnam 13620, South Korea
Hye Seung Lee, Department of Pathology, Seoul National University Hospital, Seoul 03080, South Korea
Author contributions: Ahn HM, Kim DW, Oh HJ, Kim HK, Lee HS, Lee TG, Shin HR, Yang IJ, Lee J, Suh JW, Oh HK, and Kang SB solely contributed to this paper; Ahn HM contributed to data curation, formal analysis, investigation, validation, writing-original draft, and writing-editing; Kim DW contributed to conceptualization, investigation, validation, methodology, resources, project administration, writing-review, and editing; Oh HJ contributed to investigation, resources, and methodology; Kim HK contributed to investigation, resources, and methodology; Lee HS contributed to investigation and resources; Lee TG, Shin HR, and Yang IJ contributed to data curation and validation; Lee J and Suh JW contributed to methodology and validation; Oh HK and Kang SB contributed to investigation, validation, methodology, resources, writing, review, and editing.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of Seoul National University Bundang Hospital (Approval No. B-2203-742-101).
Informed consent statement: This study was approved by the Institutional Review Board and the requirement for informed consent was waived.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: The data underlying this article will be shared upon reasonable request to the corresponding author. The data are not publicly available to protect the privacy of the participants.
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: Duck-Woo Kim, MD, PhD, Professor, Department of Surgery, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam 13620, South Korea. kdw@snubh.org
Received: May 20, 2023
Peer-review started: May 20, 2023
First decision: June 22, 2023
Revised: July 6, 2023
Accepted: July 31, 2023
Article in press: July 31, 2023
Published online: August 28, 2023
Processing time: 96 Days and 15.3 Hours
ARTICLE HIGHLIGHTS
Research background

Abnormal activation of Kirsten rat sarcoma viral oncogene homolog (KRAS), a well-known oncogene, triggers uncontrolled tumor cell proliferation. Approximately 40% of colorectal cancer (CRC) are linked to KRAS mutations. CRC -related point mutations in KRAS occur at different codon locations. KRAS codon 12 or 13 mutations are detected in a majority of CRC patients, whereas mutations in codon 61 or 146 have been reported only in a minority.

Research motivation

KRAS mutations are associated with poor CRC prognosis, especially KRAS codon 12 mutation, which is associated with metastasis and poorer survival. However, the clinicopathological characteristics and prognosis of KRAS codon 13 mutation in CRC remain controversial.

Research objectives

This study aimed to evaluate the clinicopathological characteristics and prognostic value of codon-specific KRAS mutations, especially in codon 13.

Research methods

This retrospective, single-center, observational cohort study included patients who underwent surgery for stage I-III CRC. The relationships between clinicopathological characteristics and individual codon-specific KRAS mutations were analyzed. By using the Cox proportional hazards regression model, survival analysis were performed to identify codon-specific KRAS mutations as recurrence-related factors.

Research results

Both KARS codons 12 and 13 mutations showed a tendency to be associated with clinical characteristics, but only codon 12 was associated with pathological features. KRAS codon 13 mutation showed no associations, whereas codon 12 was associated with a lower 5-year recurrence-free survival rate. In multivariable analysis, only codon 12 (HR: 1.399; 95% confidence interval: 1.034-1.894; P = 0.030) among KRAS mutations was an independent risk factor for recurrence. This may influence many oncologists to consult with patients on their prognosis after surgery.

Research conclusions

KRAS codon 12 mutation was significantly associated with pathological features closely related to cancer recurrence and had a poor prognostic impact in patients with microsatellite stable tumors, or those located in the colon but not in the rectum. On the other hand, KRAS codon 13 mutation is irrelevant to pathological features and recurrence, which consider less likely to serve as a prognostic factor for CRC.

Research perspectives

Focusing on the biological effects of codon-specific KRAS mutations, KRAS codon 13 mutation is less pathogenic and recurrent, Based on a large-scale cohort of patients with stage I-III CRC. This study’s results may influence not only the prognosis but also the management of CRC patients individually. Therefore, the therapeutic usage and needs of codon-specific KRAS mutation in CRC should be considered in future studies.