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Canadian Journal of Gastroenterology and Hepatology
Volume 2018, Article ID 4248971, 10 pages
Research Article

RAS/BRAF Circulating Tumor DNA Mutations as a Predictor of Response to First-Line Chemotherapy in Metastatic Colorectal Cancer Patients

1Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
2Beijing Novogene Bioinformatics Technology Co., Ltd., Beijing, China
3Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
4Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

Correspondence should be addressed to Mulan Jin; moc.361@narukomnik, Gang Cheng; moc.enegovon@gnehc.ffej, and Guangyu An; moc.liamtoh@uygnaugna

Received 8 November 2017; Accepted 31 January 2018; Published 7 March 2018

Academic Editor: Kiran L. Sharma

Copyright © 2018 Jiannan Yao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. Since circulating tumor DNA (ctDNA) offers clear advantages as a minimally invasive method for tumor monitoring compared with tumor tissue, we aimed to evaluate genotyping ctDNA using a next-generation sequencing- (NGS-) based panel to identify the prognostic value of mutation status in metastatic colorectal cancer (mCRC) patients with primary tumor resected and with subsequent lines of treatment in this study. Methods. 76 mCRC patients treated in Beijing Chao-Yang Hospital from 2011 to 2017 were enrolled. Genotyping of RAS/BRAF in tumor tissue and ctDNA was determined by ARMS PCR and with a 40-gene panel using NGS, respectively. Patient clinicopathologic features and RAS/BRAF gene mutation status were evaluated by survival analysis for disease-free survival (DFS) and progression-free survival (PFS). Results. Among 76 patients, KRAS distributions were not significantly correlated with any clinicopathologic features. The concordance between tumor tissue and ctDNA KRAS mutation was 81.25%. Mutations of RAS/BRAF had no significant impact on DFS after surgery (hazard ratio (HR), 1.205; 95% CI, 0.618 to 2.349; ) but prognosticated poorer PFS in subsequent first-line therapy (HR, 3.351; 95% CI, 1.172 to 9.576; ). Conclusion. ctDNA was comparable with tumor tissue for mutation detection. RAS/BRAF mutations detected in ctDNA predict a worse PFS in mCRC patients with first-line chemotherapy. Our results provide support for the prognostic value of RAS/BRAF ctDNA mutation detection in mCRC patients.