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, Chan Carlos H
Division of Hematology, Oncology and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa, USA.
Cancer Med. 2025 Aug;14(15):e71114. doi: 10.1002/cam4.71114.
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.
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.
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.
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.
突变图谱对结直肠癌（CRC）具有预后价值。具有驱动突变的大鼠肉瘤（RAS）癌基因，如KRAS和NRAS，预示着不良的生存结局，而HRAS的病理性突变极为罕见，其预后价值仍不确定。
这项回顾性研究分析了肿瘤学研究信息交换网络（ORIEN）联盟中II期和III期CRC的肿瘤RNA测序数据，以研究RAS基因表达与生存结局之间的关联。
HRAS的高转录水平与较好的总生存期（OS）相关。在右侧原发性肿瘤且KRAS转录水平低且无病理性KRAS突变的患者中，与HRAS相关的高OS获益最为明显。
与RAS家族基因是原癌基因的观点相反，本研究表明，在II期和III期CRC中，HRAS的高转录水平与较好的OS相关。应进一步探索HRAS作为预后生物标志物的潜力。
