Author/Authors :
Yao, Jiannan Department of Oncology - Beijing Chao-Yang Hospital - Capital Medical University, Beijing, China , Zang, Wanchun Beijing Novogene Bioinformatics Technology Co - Beijing, China , Ge, Yang Department of Oncology - Beijing Chao-Yang Hospital - Capital Medical University, Beijing, China , Weygant, Nathaniel Department of Medicine - Te University of Oklahoma Health Sciences Center, Oklahoma City, USA , Yu, Pan Beijing Novogene Bioinformatics Technology Co - Beijing, China , Li, Lei Beijing Novogene Bioinformatics Technology Co - Beijing, China , Rao, Guanhua Beijing Novogene Bioinformatics Technology Co - Beijing, China , Jiang, Zhi Beijing Novogene Bioinformatics Technology Co - Beijing, China , Yan, Rui Department of Oncology - Beijing Chao-Yang Hospital - Capital Medical University, Beijing, China , He, Linjia Department of Oncology - Beijing Chao-Yang Hospital - Capital Medical University, Beijing, China , Yu, Yang Beijing Novogene Bioinformatics Technology Co - Beijing, China , Jin, Mulan Department of Pathology - Beijing Chao-Yang Hospital - Capital Medical University, Beijing, China , Cheng, Gang Beijing Novogene Bioinformatics Technology Co - Beijing, China , An, Guangyu Department of Oncology - Beijing Chao-Yang Hospital - Capital Medical University, Beijing, China
Abstract :
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; P = 0.5837) but prognosticated poorer PFS in subsequent first-line therapy (HR, 3.351; 95% CI, 1.172 to 9.576; P = 0.024).
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.
