Meifang Zhang1,2,3, Wenwei Hu2, Kun Hu4, Yong Lin2,5, Zhaohui Feng2, Jing-Ping Yun1,6, Nan Gao7, Lanjing Zhang8,9,10,11. 1. Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China. 2. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. 3. Department of Pathology, Princeton Medical Center, 1 Plainsboro Rd, Plainsboro, NJ, 08536, USA. 4. Department of Pathology, University at Buffalo, Buffalo, NY, USA. 5. Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, NJ, USA. 6. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China. 7. Department of Biological Sciences, Rutgers University, Newark, NJ, USA. 8. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. lanjing.zhang@rutgers.edu. 9. Department of Pathology, Princeton Medical Center, 1 Plainsboro Rd, Plainsboro, NJ, 08536, USA. lanjing.zhang@rutgers.edu. 10. Department of Biological Sciences, Rutgers University, Newark, NJ, USA. lanjing.zhang@rutgers.edu. 11. Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA. lanjing.zhang@rutgers.edu.
Abstract
PURPOSE: To examine associations of KRAS mutation with tumor deposit status and overall survival in colorectal cancer (CRC) patients. METHODS: This retrospective cohort study included patients with incidental CRC diagnosed during 2010-2014 and recorded statuses of KRAS and tumor deposit in the National Cancer Database of the USA. Multivariable logistic regression and time-varying Cox regression analyses were used. RESULTS: We included 45,761 CRC patients with KRAS status (24,027 [52.5%] men, 24,240 [53.0%] < 65 years old, 17,338 [37.9%] with KRAS mutation). Adjusted for microsatellite instability, age, pathologic stage and tumor grade, KRAS mutation (versus wild type) was associated with tumor deposit presence (odds ratio = 1.11, 95% CI 1.02-1.20). KRAS mutation was also linked to worse overall survival of CRC patients regardless of tumor deposit status (adjusted Hazard ratio [HR] = 1.20, 95% CI 1.07-1.33 for CRC with tumor deposits, and adjusted HR = 1.24, 95% CI 1.14-1.35 or CRC without) or tumor stage (adjusted HR = 1.32, 95% CI 1.14-1.54 for early-stage and adjusted HR = 1.18, 95% CI 1.10-1.27 for late-stage). Microsatellite instability was associated with better overall survival in CRC without tumor deposit (adjusted HR = 0.89, 95% CI 0.79-0.99), but not in CRC with tumor deposit (adjusted HR = 1.12, 95% CI 0.97-1.30). CONCLUSION: KRAS mutation is independently associated with tumor deposit presence and a worse overall survival in CRC patients.
PURPOSE: To examine associations of KRAS mutation with tumor deposit status and overall survival in colorectal cancer (CRC) patients. METHODS: This retrospective cohort study included patients with incidental CRC diagnosed during 2010-2014 and recorded statuses of KRAS and tumor deposit in the National Cancer Database of the USA. Multivariable logistic regression and time-varying Cox regression analyses were used. RESULTS: We included 45,761 CRC patients with KRAS status (24,027 [52.5%] men, 24,240 [53.0%] < 65 years old, 17,338 [37.9%] with KRAS mutation). Adjusted for microsatellite instability, age, pathologic stage and tumor grade, KRAS mutation (versus wild type) was associated with tumor deposit presence (odds ratio = 1.11, 95% CI 1.02-1.20). KRAS mutation was also linked to worse overall survival of CRC patients regardless of tumor deposit status (adjusted Hazard ratio [HR] = 1.20, 95% CI 1.07-1.33 for CRC with tumor deposits, and adjusted HR = 1.24, 95% CI 1.14-1.35 or CRC without) or tumor stage (adjusted HR = 1.32, 95% CI 1.14-1.54 for early-stage and adjusted HR = 1.18, 95% CI 1.10-1.27 for late-stage). Microsatellite instability was associated with better overall survival in CRC without tumor deposit (adjusted HR = 0.89, 95% CI 0.79-0.99), but not in CRC with tumor deposit (adjusted HR = 1.12, 95% CI 0.97-1.30). CONCLUSION:KRAS mutation is independently associated with tumor deposit presence and a worse overall survival in CRC patients.
Authors: Chelain R Goodman; Brandon-Luke L Seagle; Thomas W P Friedl; Brigitte Rack; Krisztian Lato; Visnja Fink; Massimo Cristofanilli; Eric D Donnelly; Wolfgang Janni; Shohreh Shahabi; Jonathan B Strauss Journal: JAMA Oncol Date: 2018-08-09 Impact factor: 31.777
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Authors: Timothy S Maughan; Richard A Adams; Christopher G Smith; Angela M Meade; Matthew T Seymour; Richard H Wilson; Shelley Idziaszczyk; Rebecca Harris; David Fisher; Sarah L Kenny; Edward Kay; Jenna K Mitchell; Ayman Madi; Bharat Jasani; Michelle D James; John Bridgewater; M John Kennedy; Bart Claes; Diether Lambrechts; Richard Kaplan; Jeremy P Cheadle Journal: Lancet Date: 2011-06-05 Impact factor: 79.321