Lymphoma Genomic Translational Research Laboratory, Division of Medical Oncology, National Cancer Centre and Duke-NUS Medical School, Singapore 169857, Singapore
Anchalee Techasen
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Worachart Lert-itthiporn
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Sarinya Kongpetch
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Watcharin Loilome
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Jarin Chindaprasirt
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Attapol Titapun
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Nisana Namwat
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Narong Khuntikeo
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Apinya Jusakul
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
The analysis of cfDNA has been applied as a liquid biopsy in several malignancies. However, its value in the diagnosis and prognosis of cholangiocarcinoma (CCA) have not been well defined. We aimed to investigate the diagnostic and prognostic values of cfDNA level and tumor-specific mutation in circulating DNA (ctDNA) in CCA. The plasma cfDNA levels from 62 CCA patients, 33 benign biliary disease (BBD) patients and 30 normal controls were quantified by fluorescent assay. Targeted probe-based sequencing of 60 genes was applied for mutation profiling in 10 ctDNA samples and their corresponding treatment-naïve tissues. cfDNA levels in CCA were significantly higher than those in BBD and normal controls. We found that cfDNA levels at 0.2175 and 0.3388 ng/µL significantly discriminated CCA from healthy controls and BBD with 88.7 and 82.3% sensitivity and 96.7 and 57.6% specificity, respectively. cfDNA levels showed superior diagnostic efficacy in detecting CCA compared to CEA and CA19-9. ARID1A (30%), PBRM1 (30%), MTOR (30%), and FGFR3 (30%) mutations were the most common. Using nine frequently mutated genes in the ctDNA samples, the diagnostic accuracy of cfDNA sequencing was 90.8%, with 96.7% average sensitivity and 72.4% specificity. This study supports the use of cfDNA as a diagnosis and prognostic biomarker for CCA.
