KRAS Mutation and NF-κB Activation Indicates Tolerance of Chemotherapy and Poor Prognosis in Colorectal Cancer

• Published in: Digestive diseases and sciences Vol. 57; no. 9; pp. 2325 - 2333
• Main Authors: Lin, Gen, Zheng, Xiong-wei, Li, Chao, Chen, Qiang, Ye, Yun-bin
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.09.2012
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biochemistry; Biomarkers, Tumor; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Female; Gastroenterology; Gene Expression Regulation, Neoplastic; Hepatology; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; NF-kappa B - metabolism; Oncology; Original Article; Pneumoviridae; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; ras Proteins - metabolism; Retrospective Studies; Transplant Surgery; NF-κB; Chemotherapy; KRAS; Prognosis; Colorectal carcinoma
• ISSN: 0163-2116; 1573-2568; 1573-2568
• DOI: 10.1007/s10620-012-2172-x

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.