Proto‐Oncogene HRAS Transcript Level and Overall Survival in Stages II and III Colorectal Cancer

Donghyun Kim; Saima Sharif; Juan Antonio Raygoza Garay; Avanish S. Bhakta; Patrick M. Boland; Michael J. Cavnar; Michelle L. Churchman; Hassan Hatoum; Lyen C. Huang; Joseph Kim; Richard Kim; Robert W. Lentz; Sarbajit Mukherjee; Mary T. O'Donnell; Benjamin Quartey; Matthew J. Reilley; Robert J. Rounbehler; Bodour Salhia; Bryan P. Schneider; Carlos H. Chan

doi:10.1002/cam4.71114

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Proto‐Oncogene HRAS Transcript Level and Overall Survival in Stages II and III Colorectal Cancer

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Proto‐Oncogene HRAS Transcript Level and Overall Survival in Stages II and III Colorectal Cancer

Donghyun Kim, Saima Sharif, Juan Antonio Raygoza Garay, Avanish S. Bhakta, Patrick M. Boland, Michael J. Cavnar, Michelle L. Churchman, Hassan Hatoum, Lyen C. Huang, Joseph Kim, …

Cancer medicine (Malden, MA), Vol.14(15), e71114

07/31/2025

DOI: 10.1002/cam4.71114

PMCID: PMC12311480

PMID: 40879062

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Abstract

Background Mutational landscape is prognostic in colorectal cancer (CRC). Rat sarcoma (RAS) oncogenes, such as KRAS and NRAS, with driver mutations, portend poor survival outcomes, whereas pathologic mutations in HRAS are extremely rare, and their prognostic value remains uncertain. Methods This retrospective study analyzed the Oncology Research Information Exchange Network (ORIEN) alliance tumor RNA-Seq data in Stages II and III CRC to investigate the association between RAS gene expression and survival outcomes. Results High transcript levels of HRAS were associated with superior overall survival (OS). The high HRAS-associated OS benefit was most pronounced in patients with right-sided primary expressing low KRAS transcript levels in the absence of pathologic KRAS mutations. Conclusions Contrary to the notion that RAS family genes are proto-oncogenic, this study demonstrates that high HRAS transcript levels are associated with superior OS in Stages II and III CRC. The potential of HRAS as a prognostic biomarker should be explored further.

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Title: Subtitle: Proto‐Oncogene HRAS Transcript Level and Overall Survival in Stages II and III Colorectal Cancer
Creators: Donghyun Kim - University of Iowa
Saima Sharif - University of Iowa
Juan Antonio Raygoza Garay - University of Iowa, Holden Comprehensive Cancer Center
Avanish S. Bhakta - University of Kentucky
Patrick M. Boland - Rutgers, The State University of New Jersey
Michael J. Cavnar - University of Kentucky
Michelle L. Churchman
Hassan Hatoum - University of Oklahoma Health Sciences Center
Lyen C. Huang - Huntsman Cancer Institute
Joseph Kim - University of Kentucky
Richard Kim - Moffitt Cancer Center
Robert W. Lentz - University of Colorado Anschutz Medical Campus
Sarbajit Mukherjee - Roswell Park Comprehensive Cancer Center
Mary T. O'Donnell - Walter Reed National Military Medical Center
Benjamin Quartey - Walter Reed National Military Medical Center
Matthew J. Reilley - University of Virginia
Robert J. Rounbehler - Aster Insights
Bodour Salhia - University of Southern California
Bryan P. Schneider - Indiana University – Purdue University Indianapolis
Carlos H. Chan - University of Iowa, Surgery
Resource Type: Journal article
Publication Details: Cancer medicine (Malden, MA), Vol.14(15), e71114
DOI: 10.1002/cam4.71114
PMID: 40879062
PMCID: PMC12311480
NLM abbreviation: Cancer Med
ISSN: 2045-7634
eISSN: 2045-7634
Publisher: Wiley
Language: English
Date published: 07/31/2025
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Surgery; Radiation Oncology; Holden Comprehensive Cancer Center; Internal Medicine
Record Identifier: 9984927216902771

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