Abdelgadir O, Kuo YF, Khan MF, Okorodudu AO, Cheng YWO, Dong J. Colorectal cancer tumor phenotypes associated with KRAS, NRAS, and BRAF hot-spot mutations. World J Gastrointest Pathophysiol 2025; 16(3): 107954 [PMID: 41024990 DOI: 10.4291/wjgp.v16.i3.107954]
Corresponding Author of This Article
Jianli Dong, MD, PhD, Professor, Department of Pathology, Director, Molecular Diagnostics Division, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, United States. jidong@utmb.edu
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Pathophysiol. Sep 22, 2025; 16(3): 107954 Published online Sep 22, 2025. doi: 10.4291/wjgp.v16.i3.107954
Colorectal cancer tumor phenotypes associated with KRAS, NRAS, and BRAF hot-spot mutations
Omer Abdelgadir, Yong-Fang Kuo, M Firoze Khan, Anthony O Okorodudu, Yu-Wei O Cheng, Jianli Dong
Omer Abdelgadir, Graduate School of Biomedical Science, University of Texas Medical Branch, Galveston, TX 77555, United States
Yong-Fang Kuo, School of Public and Population Health, University of Texas Medical Branch, Galveston, TX 77555, United States
M Firoze Khan, Anthony O Okorodudu, Jianli Dong, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, United States
Yu-Wei O Cheng, Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH 44106, United States
Author contributions: Abdelgadir OA and Dong J designed the research study; Abdelgadir O, Kuo YF, and Dong J performed and validate the statistical analysis; Abdelgadir O, Kuo YF, Khan MF, Okorodudu AO, Cheng YWO, and Dong J performed the manuscript writing, review and editing; and all authors have read and agreed to the published version of the manuscript.
Institutional review board statement: This study was approved by the Medical Ethics Committee of University of Texas Medical Branch, approval No. 02-089.
Informed consent statement: No patient informed consent specific to this study was required due to the retrospective nature of the study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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.
Data sharing statement: The data presented in this study are de-identified and available upon reasonable request from the corresponding author. The data are not publicly available due to patient confidentiality restrictions.
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: Jianli Dong, MD, PhD, Professor, Department of Pathology, Director, Molecular Diagnostics Division, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, United States. jidong@utmb.edu
Received: April 2, 2025 Revised: May 19, 2025 Accepted: August 1, 2025 Published online: September 22, 2025 Processing time: 171 Days and 15.2 Hours
Abstract
BACKGROUND
Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) nucleotide variants may generate quantitatively or qualitatively various protein activities, which may be reflected in their differential association with tumor characteristics.
AIM
To examine the association between these mutations and colorectal cancer (CRC) progression stages.
METHODS
A retrospective analysis was conducted on 799 patients with CRC, whose tumor samples were examined for mutations in the hot-spots of the KRAS, NRAS, and BRAF genes at the University of Texas Medical Branch, spanning from January 2016 to July 2023. Statistical analyses were performed to assess the association of specific nucleotide changes with tumor, nodes, and metastasis stages.
RESULTS
KRAS mutations were found in 39.5% of cases, NRAS mutations in 4.4%, and BRAF mutations in 6.0%. The KRAS p.Gly12Val and p.Gly13Asp mutations were positively associated with pathological stage 4 tumors. Additionally, the KRAS p.Gly12Asp and p.Gly12Val mutations were linked to an increased risk of distant metastasis. Meanwhile, the BRAF Val600Glu mutation was associated with a higher likelihood of lymph node involvement.
CONCLUSION
Our findings support the potential prognostic utility of specific KRAS (p.Gly12Val, p.Gly12Asp, and p.Gly13Asp) and BRAF p.Val600Glu mutations in CRC. These results are preliminary and require validation through larger, multi-center studies before they can be considered reliable in clinical practice.
Core Tip: In colorectal cancer, the kirsten rat sarcoma viral oncogene homolog p.Gly12Val and p.Gly13Asp mutations were linked to advanced tumor stage, while the kirsten rat sarcoma viral oncogene homolog p.Gly12Asp and p.Gly12Val mutations showed a positive association with distant metastasis. The v-raf murine sarcoma viral oncogene homolog B1 p.Val600Glu mutation was associated with lymph node metastasis. This study provides evidence to support the prognostic and risk stratification potential of these mutations. Further studies are needed to validate these findings and explore their clinical implications for patients with colorectal cancer.
