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

Authors

• Donghyun Kim, University of Iowa Carver College of MedicineFollow
• Saima Sharif, University of Iowa Carver College of Medicine
• Juan Antonio Raygoza Garay, University of Iowa Hospitals and Clinics
• Avanish S. Bhakta, University of Kentucky College of MedicineFollow
• Patrick M. Boland, Rutgers - The State University of New Jersey, New Brunswick
• Michael J. Cavnar, University of KentuckyFollow
• Michelle L. Churchman, Aster Insights
• Hassan Hatoum, University of Oklahoma
• Lyen C. Huang, University of Utah
• Joseph Kim, University of KentuckyFollow
• Richard Kim, University of South Florida
• Robert W. Lentz, University of Colorado Hospital Denver
• Sarbajit Mukherjee, Roswell Park Cancer Institute
• Mary T. O'Donnell, Walter Reed Army Institute of Research
• Benjamin Quartey, Walter Reed Army Institute of Research
• Matthew J. Reilley, University of Virginia
• Robert J. Rounbehler, Aster Insights
• Bodour Salhia, University of Southern California
• Bryan P. Schneider, Indiana University
• Carlos H. Chan, University of Iowa Carver College of MedicineFollow

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.

Document Type

Article

Publication Date

8-1-2025

Notes/Citation Information

Publisher Copyright: © 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

Digital Object Identifier (DOI)

10.1002/cam4.71114

Archival?

Archival

Repository Citation

Kim, Donghyun; Sharif, Saima; Garay, Juan Antonio Raygoza; Bhakta, Avanish S.; Boland, Patrick M.; Cavnar, Michael J.; Churchman, Michelle L.; Hatoum, Hassan; Huang, Lyen C.; Kim, Joseph; Kim, Richard; Lentz, Robert W.; Mukherjee, Sarbajit; O'Donnell, Mary T.; Quartey, Benjamin; Reilley, Matthew J.; Rounbehler, Robert J.; Salhia, Bodour; Schneider, Bryan P.; and Chan, Carlos H., "Proto-Oncogene HRAS Transcript Level and Overall Survival in Stages II and III Colorectal Cancer" (2025). Surgery Faculty Publications. 78.
https://uknowledge.uky.edu/surgery_facpub/78