Abstract
Simple SummaryCirculating tumor DNA (ctDNA) is a minimally invasive biomarker useful for monitoring minimum residual disease, recurrence, and treatment response in colorectal cancer (CRC). We analyzed circulating tumor DNA from patients with CRC to evaluate analytical and clinical performances using next-generation sequencing (NGS). It is clear that postoperative circulating tumor DNA detection provides valuable information to determine whether a patient might at high risk of disease recurrence or have a persistent tumor lesion. The NGS assay not only showed excellent analytical performance, but also shows a state-of-art diagnostic option in patient-oriented precision medicine.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%). TP53 mutations were the most frequent (17 of 49 patients, 34.7%), followed by APC (18.4%), KRAS (12.2%), FBXW7 (8.2%), NRAS (2.0%), PIK3CA (2.0%), and SMAD4 (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.
Highlights
Circulating tumor DNA, known as tumor-derived cell-free DNA, can be detected in the acellular part of peripheral blood from cancer patients [1]
The potential of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) as a minimally invasive biomarker has been highlighted in many recent studies for treatment response, prognosis prediction, minimum residual disease (MRD), and recurrence monitoring [9,10,11,12,13,14,15,16,17,18]. ctDNA profiling can effectively reveal the genomic landscape of cancer compared to tissue profiling by reflecting heterogeneity and providing biologically essential findings including therapeutic resistance [9]
Mutations observed at diagnosis can be used as MRD markers to evaluate therapeutic response and predict patient prognosis related to recurrence and survival, allowing appropriate timing for ctDNA testing before and/or after treatment [14,15,16,17,18]
Summary
Circulating tumor DNA (ctDNA), known as tumor-derived cell-free DNA (cfDNA), can be detected in the acellular part of peripheral blood from cancer patients [1]. CtDNA profiling can effectively reveal the genomic landscape of cancer compared to tissue profiling by reflecting heterogeneity and providing biologically essential findings including therapeutic resistance [9]. The potential of ctDNA in colorectal cancer (CRC) as a minimally invasive biomarker has been highlighted in many recent studies for treatment response, prognosis prediction, minimum residual disease (MRD), and recurrence monitoring [9,10,11,12,13,14,15,16,17,18]. This is useful for rapidly identifying resistance-causing mutations and for selecting therapeutic agents [10,11,12,13]. There are several ongoing randomized trials worldwide to determine the clinical utility of ctDNA in colorectal cancer [20]
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