To investigate whether mutation profiling and microsatellite instability (MSI) status were associated with clinicopathological features and the prognosis in metastatic colorectal cancer (mCRC), mutations in RAS (including KRAS, NRAS, and HRAS) and BRAF were determined by Sanger sequencing. Tumor mismatch repair proteins and MSI status were examined using immunohistochemistry and polymerase chain reaction, respectively. The clinical value of these abnormalities was statistically analyzed, and prognostic value of different treatment regimens was also evaluated. Among 461 mCRC patients, mutations in RAS, BRAF, and MSI-high (MSI-H) status were observed in 45.3% (209/461), 5.6% (26/461), and 6.5% (30/461) of cases, respectively. Brain metastasis and high carcinoembryonic antigen level were highly correlated with KRAS mutation (P = 0.011 and P < 0.001), and tumors from females or located in the right colon tended to harbor BRAF mutation (P = 0.039 and P = 0.001). RAS/BRAF mutations may predict brain and/or lung metastases. Although neither clinical nor prognostic importance of MSI status was identified in our study, KRAS and BRAF mutations were demonstrated to be independent prognostic factors for overall survival and progression-free survival. Besides, in wild-type group, patients treated with chemotherapy plus targeted therapy exhibited the most favorable prognosis. Therefore, RAS/BRAF mutations may serve as indicators for prognosis and treatment options in mCRC.

No abstract

The present study aimed to investigate whether c-mesenchymal epithelial transition factor (C-MET) overexpression combined with RAS (including KRAS, NRAS and HRAS) or BRAF mutations were associated with late distant metastases and the prognosis of patients with colorectal cancer (CRC). A total of 374 patients with stage III CRC were classified into 4 groups based on RAS/BRAF and C-MET status for comprehensive analysis. Mutations in RAS/BRAF were determined using Sanger sequencing and C-MET expression was examined using immunohistochemistry. The associations between RAS/BRAF mutations in combination with C-MET overexpression and clinicopathological variables including survival were evaluated. In addition, their predictive value for late distant metastases were statistically analyzed via logistic regression and receiver operating characteristic analysis. Among 374 patients, mutations in KRAS, NRAS, HRAS, BRAF and C-MET overexpression were observed in 43.9, 2.4, 0.3, 5.9 and 71.9% of cases, respectively. Considering RAS/BRAF mutations and C-MET overexpression, vascular invasion (P=0.001), high carcino-embryonic antigen level (P=0.031) and late distant metastases (P<0.001) were more likely to occur in patients of group 4. Furthermore, survival analyses revealed RAS/BRAF mutations may have a more powerful impact on survival than C-MET overexpression, although they were both predictive factors for adverse prognosis. Further logistic regression suggested that RAS/BRAF mutations and C-MET overexpression may predict late distant metastases. In conclusion, RAS/BRAF mutations and C-MET overexpression may serve as predictive indicators for metastatic behavior and poor prognosis of CRC.