Postoperative Circulating Tumor DNA Can Predict High Risk Patients with Colorectal Cancer Based on Next-Generation Sequencing

• Main Authors: Chul Seung Lee, Hoon Seok Kim, Jeoffrey Schageman, In Kyu Lee, Myungshin Kim, Yonggoo Kim
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Cancers
• Subjects: circulating tumor DNA; colorectal cancer; next-generation sequencing
• Online Access: https://www.mdpi.com/2072-6694/13/16/4190

The objective of this study was to characterize circulating tumor DNA (ctDNA) mutations in colorectal cancer (CRC) patients and evaluate their prognostic values during treatment. Forty-nine patients with CRC planned for operation were enrolled. A total of 115 plasma samples were collected pre-operation, post-operation, and post-chemotherapy. ctDNA analysis was performed using next-generation sequencing (NGS) including 14 genes. In 22 (44.9%) out of 49 patients, at least one mutation (40 total mutations) was detected in the initial plasma sample. The median sum of variant allele frequency was 0.74% (range: 0.10–29.57%). <i>TP53</i> mutations were the most frequent (17 of 49 patients, 34.7%), followed by <i>APC</i> (18.4%), <i>KRAS</i> (12.2%), <i>FBXW7</i> (8.2%), <i>NRAS</i> (2.0%), <i>PIK3CA</i> (2.0%), and <i>SMAD4</i> (2.0%). After surgery, five (14.3%) out of 35 patients harbored ctDNA mutation. All five patients experienced relapse or metastasis during follow-up. It was noteworthy that all three patients with persistent ctDNA relapsed after R0 resection. After chemotherapy, ctDNA analysis was performed for 31 patients, all of which were ctDNA-negative. Analytical and clinical performances of NGS to utilize ctDNA in CRC were determined. Results revealed that postoperative ctDNA might serve as a marker for identifying risk of recurrence, thus contributing to patient-oriented treatment strategies.