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

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.