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
Abstract
BACKGROUND

Approximately 40% of colorectal cancer (CRC) cases are linked to Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. 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 unclear.

AIM

To evaluate the clinicopathological characteristics and prognostic value of codon-specific KRAS mutations, especially in codon 13.

METHODS

This retrospective, single-center, observational cohort study included patients who underwent surgery for stage I-III CRC between January 2009 and December 2019. Patients with KRAS mutation status confirmed by molecular pathology reports were included. The relationships between clinicopathological characteristics and individual codon-specific KRAS mutations were analyzed. Survival data were analyzed to identify codon-specific KRAS mutations as recurrence-related factors using the Cox proportional hazards regression model.

RESULTS

Among the 2203 patients, the incidence of KRAS codons 12, 13, and 61 mutations was 27.7%, 9.1%, and 1.3%, respectively. 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, such as stage of primary tumor (T stage), lymph node involvement (N stage), vascular invasion, perineural invasion, tumor size, and microsatellite instability. KRAS codon 13 mutation showed no associations (77.2% vs 85.3%, P = 0.159), whereas codon 12 was associated with a lower 5-year recurrence-free survival rate (78.9% vs 75.5%, P = 0.025). In multivariable analysis, along with T and N stages and vascular and perineural invasion, only codon 12 (hazard ratio: 1.399; 95% confidence interval: 1.034-1.894; P = 0.030) among KRAS mutations was an independent risk factor for recurrence.

CONCLUSION

This study provides evidence that KRAS codon 13 mutation is less likely to serve as a prognostic biomarker than codon 12 mutation for CRC in a large-scale cohort.

Keywords: Genes; Ras; Codon; Colonic neoplasms; Rectal neoplasms

Core Tip: Based on a large-scale cohort of patients with stage I-III colorectal cancer (CRC), Kirsten rat sarcoma viral oncogene homolog (KRAS) codon 13 mutation is less pathogenic and recurrent. Moreover, focusing on the biological effects of codon-specific KRAS mutations and minimizing interference with various medical therapies, previous in vivo studies demonstrating that KRAS codon 13 mutation is less aggressive were translated into clinical outcomes in this study. This may influence many oncologists to consult with patients on their prognosis after surgery. We propose that KRAS codon 13 mutation is less likely to serve as a prognostic factor of CRC, compared with codon 12.