BACKGROUND: Evidence shows a strong relationship between KRAS mutations and the NF-κB signaling pathway. In colorectal cancer, however, the study of this subject has been very limited and results are inconsistent. AIMS: To examine the relationship between KRAS mutations and NF-κB activation and their effect on chemotherapy response and survival of colorectal cancer patients. MATERIALS AND METHODS: NF-κB activation was analyzed by immunohistochemistry in 167 primary colorectal cancer specimens in which the KRAS mutation status was confirmed. Clinical and pathologic data were extracted from the medical records and reviewed. RESULTS: Of 167 tumors screened, 63 (37.7 %) had NF-κB activation, 59 (35.3 %) had KRAS mutations, and 30 (18.0 %) had both NF-κB activation and KRAS mutations. The frequency of NF-κB activation in tumors with KRAS mutations was significantly higher than in tumors with wild type KRAS; 50.8 versus 30.6 %, P = 0.012. Patients with both KRAS mutations and NF-κB activation had a lower objective response to first-line chemotherapy than patients with other tumors, 23.8 versus 49.4 % (P = 0.035). Compared to patients with both KRAS mutations and NF-κB activation, overall survival of patients in other groups was significantly higher; median overall survival was 28.4 months (95 % CI 21.0-35.8) versus 46.3 months (95 % CI 39.4-53.2), hazard ratio 0.259 (95 % CI 0.125-0.538), P = 0.005. CONCLUSIONS: NF-κB activation was associated with KRAS mutation, and both KRAS mutation and NF-κB activation were indicative of high tolerance of chemotherapy and poor prognosis for colorectal cancer patients. Tumors with KRAS mutations and NF-κB activation may be a unique subtype of colorectal cancer.
BACKGROUND: Evidence shows a strong relationship between KRAS mutations and the NF-κB signaling pathway. In colorectal cancer, however, the study of this subject has been very limited and results are inconsistent. AIMS: To examine the relationship between KRAS mutations and NF-κB activation and their effect on chemotherapy response and survival of colorectal cancerpatients. MATERIALS AND METHODS: NF-κB activation was analyzed by immunohistochemistry in 167 primary colorectal cancer specimens in which the KRAS mutation status was confirmed. Clinical and pathologic data were extracted from the medical records and reviewed. RESULTS: Of 167 tumors screened, 63 (37.7 %) had NF-κB activation, 59 (35.3 %) had KRAS mutations, and 30 (18.0 %) had both NF-κB activation and KRAS mutations. The frequency of NF-κB activation in tumors with KRAS mutations was significantly higher than in tumors with wild type KRAS; 50.8 versus 30.6 %, P = 0.012. Patients with both KRAS mutations and NF-κB activation had a lower objective response to first-line chemotherapy than patients with other tumors, 23.8 versus 49.4 % (P = 0.035). Compared to patients with both KRAS mutations and NF-κB activation, overall survival of patients in other groups was significantly higher; median overall survival was 28.4 months (95 % CI 21.0-35.8) versus 46.3 months (95 % CI 39.4-53.2), hazard ratio 0.259 (95 % CI 0.125-0.538), P = 0.005. CONCLUSIONS: NF-κB activation was associated with KRAS mutation, and both KRAS mutation and NF-κB activation were indicative of high tolerance of chemotherapy and poor prognosis for colorectal cancerpatients. Tumors with KRAS mutations and NF-κB activation may be a unique subtype of colorectal cancer.
Authors: Wendy De Roock; Derek J Jonker; Federica Di Nicolantonio; Andrea Sartore-Bianchi; Dongsheng Tu; Salvatore Siena; Simona Lamba; Sabrina Arena; Milo Frattini; Hubert Piessevaux; Eric Van Cutsem; Chris J O'Callaghan; Shirin Khambata-Ford; John R Zalcberg; John Simes; Christos S Karapetis; Alberto Bardelli; Sabine Tejpar Journal: JAMA Date: 2010-10-27 Impact factor: 56.272
Authors: A Cadoret; F Bertrand; S Baron-Delage; P Lévy; G Courtois; C Gespach; J Capeau; G Cherqui Journal: Oncogene Date: 1997-04-03 Impact factor: 9.867
Authors: E Ramsay Camp; Jing Li; Douglas J Minnich; Adam Brank; Lyle L Moldawer; Sally L D MacKay; Steven N Hochwald Journal: J Am Coll Surg Date: 2004-08 Impact factor: 6.113
Authors: Md Sanower Hossain; Md Abdul Kader; Khang Wen Goh; Maidul Islam; Md Sharif Khan; Md Harun-Ar Rashid; Der Jiun Ooi; Henrique Douglas Melo Coutinho; Yaser Mohammed Al-Worafi; Said Moshawih; Ya Chee Lim; K M Kaderi Kibria; Long Chiau Ming Journal: Front Pharmacol Date: 2022-06-30 Impact factor: 5.988