{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:30:43Z","timestamp":1790173843271,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Mutational landscape is prognostic in colorectal cancer (CRC).\n Rat sarcoma<\/jats:italic>\n (\n RAS<\/jats:italic>\n ) oncogenes, such as\n KRAS<\/jats:italic>\n and\n NRAS<\/jats:italic>\n , with driver mutations, portend poor survival outcomes, whereas pathologic mutations in\n HRAS<\/jats:italic>\n are extremely rare, and their prognostic value remains uncertain.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This retrospective study analyzed the Oncology Research Information Exchange Network (ORIEN) alliance tumor RNA\u2010Seq data in Stages II and III CRC to investigate the association between\n RAS<\/jats:italic>\n gene expression and survival outcomes.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n High transcript levels of\n HRAS<\/jats:italic>\n were associated with superior overall survival (OS). The high\n HRAS<\/jats:italic>\n \u2010associated OS benefit was most pronounced in patients with right\u2010sided primary expressing low\n KRAS<\/jats:italic>\n transcript levels in the absence of pathologic\n KRAS<\/jats:italic>\n mutations.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Contrary to the notion that\n RAS<\/jats:italic>\n family genes are proto\u2010oncogenic, this study demonstrates that high\n HRAS<\/jats:italic>\n transcript levels are associated with superior OS in Stages II and III CRC. The potential of\n HRAS<\/jats:italic>\n as a prognostic biomarker should be explored further.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cam4.71114","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T09:17:58Z","timestamp":1753953478000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Proto\u2010Oncogene\n HRAS<\/i>\n Transcript Level and Overall Survival in Stages\n II<\/scp>\n and\n III<\/scp>\n Colorectal Cancer"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6998-302X","authenticated-orcid":false,"given":"Donghyun","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Hematology, Oncology and Blood & Marrow Transplantation, Department of Internal Medicine University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saima","family":"Sharif","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology and Blood & Marrow Transplantation, Department of Internal Medicine University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio Raygoza","family":"Garay","sequence":"additional","affiliation":[{"name":"Holden Comprehensive Cancer Center, University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avanish S.","family":"Bhakta","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4213-8847","authenticated-orcid":false,"given":"Patrick M.","family":"Boland","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Rutgers Cancer Institute of New Jersey New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Cavnar","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Churchman","sequence":"additional","affiliation":[{"name":"Department of Clinical & Life Sciences Aster Insights Hudson Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Hatoum","sequence":"additional","affiliation":[{"name":"Section of Hematology\u2010Oncology, Department of Internal Medicine University of Oklahoma Health Sciences Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8605-2631","authenticated-orcid":false,"given":"Lyen C.","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, Huntsman Cancer Institute University of Utah Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology Moffitt Cancer Center Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Lentz","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine University of Colorado Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarbajit","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine Roswell Park Comprehensive Cancer Center Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary T.","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Department of General Surgery Walter Reed National Military Medical Center Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Quartey","sequence":"additional","affiliation":[{"name":"Department of General Surgery Walter Reed National Military Medical Center Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Reilley","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine University of Virginia Comprehensive Cancer Center Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Rounbehler","sequence":"additional","affiliation":[{"name":"Department of Clinical & Life Sciences Aster Insights Hudson Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodour","family":"Salhia","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan P.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Indiana University Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos H.","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology and Endocrine Surgery, Department of Surgery University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"AJCC Cancer Staging Manual","author":"Amin M. 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