Independent prognostic value of KRAS mutation in resected colorectal cancer based on multi-gene sequencing

doi:10.4251/wjgo.v18.i6.117308

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Jun 15, 2026; 18(6): 117308
Published online Jun 15, 2026. doi: 10.4251/wjgo.v18.i6.117308

Independent prognostic value of KRAS mutation in resected colorectal cancer based on multi-gene sequencing

Sheng-Qiang Zhao, Zhao-Feng Luo, Zhan-Feng Yang, Wei-Shan Zhang, Yu-Ming Fu

Sheng-Qiang Zhao, Zhao-Feng Luo, Zhan-Feng Yang, Wei-Shan Zhang, Yu-Ming Fu, Department of Gastrointestinal and Thyroid Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China

Co-first authors: Sheng-Qiang Zhao and Zhao-Feng Luo.

Author contributions: Zhao SQ and Luo ZF conceived the study and drafted the manuscript as co-first authors; Luo ZF and Yang ZF performed the experiments and data analysis; Zhang WS contributed to data processing and visualization; Fu YM supervised the research and revised the manuscript; all authors reviewed and approved the final version of the manuscript.

AI contribution statement: During the preparation of the manuscript, we used the DeepSeek tool. The entire main text of the manuscript (including the Abstract, Introduction, Materials and Methods, Results, Discussion, and Conclusion) was independently written by ourselves and was not generated by AI. The AI tool did not contribute to any of the core academic content. During the final revision stage of the manuscript, we used DeepSeek for language polishing and refinement, primarily to improve the fluency and clarity of certain expressions. All research data, conclusions, logic, and academic viewpoints are entirely our own. No AI tool was used in the design of the study or the interpretation of the results. All figures in the manuscript are either charts generated from raw data or schematic diagrams. No images were generated by AI.

Supported by Molecular Mechanism by the Henan Provincial Health and Wellness Committee, No. SBGJ202102184.

Institutional review board statement: This retrospective study was approved by the Ethics Committee of the Fifth Affiliated Hospital of Zhengzhou University (No. KY2025034-K02). All procedures were conducted in accordance with the ethical standards of the institutional and national research committees and with the Declaration of Helsinki.

Informed consent statement: All participants provided informed consent.

Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.

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 datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.

Corresponding author: Yu-Ming Fu, MD, Department of Gastrointestinal and Thyroid Surgery, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Kangfu Qian Street, Erqi District, Zhengzhou 450052, Henan Province, China. yumingfu0204@126.com

Received: December 4, 2025
Revised: December 24, 2025
Accepted: February 3, 2026
Published online: June 15, 2026
Processing time: 187 Days and 19.2 Hours

Abstract

BACKGROUND

Colorectal cancer (CRC) shows marked molecular heterogeneity, yet the clinicopathological and prognostic utility of routinely tested driver mutations in resected CRC remains incompletely defined.

AIM

To evaluate the associations of KRAS, PIK3CA, FBXW7, and TP53 mutations with clinicopathological features and overall survival (OS) in patients with curatively resected CRC.

METHODS

We retrospectively analyzed 87 patients who underwent curative-intent CRC resection (2015-2020). Mutations in KRAS, PIK3CA, FBXW7, and TP53 were assessed using next-generation sequencing on formalin-fixed, paraffin-embedded tumor samples. Associations with clinicopathological variables were tested using appropriate categorical/continuous analyses. OS was evaluated by Kaplan-Meier/log-rank methods and Cox regression. Median follow-up was 60 months (cutoff: April 2025).

RESULTS

Mutation frequencies were KRAS of 44.8%, PIK3CA of 13.8%, FBXW7 of 27.6%, and TP53 of 64.4%. KRAS mutation clustered with adverse phenotypes (including perineural invasion, nodal/distant metastasis, multifocality, larger tumor size, and elevated tumor markers). PIK3CA mutation correlated with larger tumor diameter, while FBXW7 and TP53 showed selective clinicopathological associations. The 3-year and 5-year OS rates were 63.2% and 41.4%, respectively. KRAS mutation independently predicted worse OS (hazard ratio = 3.57), whereas PIK3CA mutation showed a protective association (hazard ratio = 0.26); FBXW7 and TP53 were not independent prognostic factors.

CONCLUSION

In resected CRC, KRAS mutation delineates a high-risk subgroup with inferior survival, supporting routine KRAS genotyping to enhance postoperative risk stratification and surveillance planning; larger, prospectively profiled cohorts are warranted to refine multi-gene prognostic models.

Keywords: Colorectal cancer; Gene mutation; KRAS; TP53; Prognosis

Core Tip: This study used multi-gene next-generation sequencing in a resected colorectal cancer cohort to compare the clinicopathological and prognostic impact of KRAS, PIK3CA, FBXW7, and TP53 mutations. We found that KRAS mutation defines an aggressive phenotype and is an independent predictor of poor long-term survival, whereas PIK3CA, FBXW7, and TP53 mutations provide limited standalone prognostic information. These findings support routine KRAS genotyping for perioperative risk stratification and suggest that other recurrent mutations should be interpreted within integrated molecular models rather than in isolation.