Objective: To investigate the connection between mutant KRAS/NRAS/BRAF  and clinicopathological characteristics in therapy-naïve synchronous metastatic colorectal cancer (mCRC) in Chinese populations when compared with all wild type (KRAS/NRAS/BRAF  wild type).
Patients and Methods: A total of 200 patients with therapy-naïve synchronous mCRC (TNM stage: TanyNanyM1) were retrospectively collected as study objects. Primary tumor tissues from 200 mCRC patients were analyzed through next-generation sequencing panel to assess the mutated regions of KRAS/NRAS/BRAF .
Results: The distribution frequency of gene mutation in our study was 41% KRAS , 4% NRAS , 11.5% BRAF , 0.5% both KRAS  and BRAF . Tumors with any gene mutations (any gene mutations in KRAS/NRAS/BRAF ), KRAS  and KRAS codon 12  mutation were more likely to be located in right-sided colon (P=0.007, P=0.008, P=0.026, respectively). For metastasis, tumors with any gene mutations, KRAS  and KRAS codon 12  mutation were significantly correlated with peritoneal metastasis (P=0.019, P=0.017, P=0.014, respectively), liver-peritoneum metastases (P=0.004, P=0.003, P=0.002, respectively) and multi-organ metastases (P=0.002, P=0.008, P=0.001, respectively). Tumors with all wild type were significantly correlated with distant lymph node-only metastasis. No statistically significant differences were found between clinicopathological characteristics and KRAS codon 13  and NRAS  mutations.
Conclusion: Our study suggests that clinicopathological characteristics (specifically for metastasis) are related to KRAS/NRAS/BRAF  mutations in therapy-naïve synchronous mCRC population in China. We demonstrated that distant lymph node-only metastasis is visibly linked to all wild-type tumors. We found that patients with any gene mutations, KRAS  mutation are more likely to carry peritoneal metastasis, liver-peritoneum metastases and multi-organ metastases than those with all wild type. After stratification, KRAS codon 12  mutation, but not codon 13  mutation, was remarkably associated with peritoneal metastasis, liver-peritoneum metastases, and multi-organ metastases compared to all wild type. These results may be useful for aiding in the prediction of prognosis and choosing the appropriate regimens for therapy.
Keywords: synchronous metastatic colorectal cancer, KRAS  mutation, NRAS  mutation, BRAF  mutation, KRAS codon 12  mutation, KRAS codon 13  mutation