OncoTargets and Therapy (Dec 2020)
KRAS Codon 12 Mutation is Associated with More Aggressive Invasiveness in Synchronous Metastatic Colorectal Cancer (mCRC): Retrospective Research
Abstract
Kang He,1,* Yajing Wang,1,* Yuejiao Zhong,2 Xiaohua Pan,1 Lixiang Si,1 Jianwei Lu1 1The Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, People’s Republic of China; 2The Department of Oncology, Jiangsu Cancer Hospital, and the Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Institute of Cancer Research, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianwei LuThe Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, People’s Republic of ChinaEmail [email protected]: 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
