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Circulating Tumor DNA as a Biomarker for Predicting and Monitoring CCA
1 Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
2 Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences,
Khon Kaen University, Khon Kaen, Thailand
3 Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
4 Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen,
Thailand
5 Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
Background and Aims: Circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) have emerged as valuable
biomarkers in various cancers, including biliary tract cancers. We aimed to investigate the diagnostic and prognostic
potential of cfDNA compared to traditional serum protein tumor markers in cholangiocarcinoma (CCA) patients.
Additionally, the study sought to explore the feasibility of ctDNA sequencing for genetic profiling and its correlation with
treatment response and patient survival.
Results: The results demonstrated that cfDNA levels were significantly elevated in CCA patients compared to the healthy
individual and patients with benign biliary diseases. Moreover, increased cfDNA levels were associated with tumor
progression in CCA. Importantly, the diagnostic efficacy of cfDNA levels surpassed that of commonly used tumor markers,
CA19-9 and CEA, in CCA diagnosis. These findings highlight the potential of cfDNA analysis as a reliable tool for CCA
diagnosis and prognosis. Furthermore, ctDNA sequencing revealed the presence of tumor-specific genetic alterations in
CCA patients, with a high concordance between ctDNA mutations and corresponding tumor tissues. Notably, KRAS
mutations were highly prevalent in CCA and could be detected using liquid biopsy, specifically in ctDNA. Combining KRAS
mutation detection in ctDNA with CA19-9 levels improved the diagnosis of CCA. Moreover, CCA patients with high KRAS
mutation frequency and elevated CA19-9 levels in plasma exhibited a poor prognosis.
Conclusion: The use of cfDNA analysis and ctDNA sequencing holds great potential for enhancing the clinical management
of CCA, facilitating early diagnosis, and guiding treatment decisions. These results contribute to the growing body of
evidence supporting the value of cfDNA as a diagnostic and prognostic marker in biliary tract cancers, particularly CCA.
This research was supported by NSRF under the Basic Research Fund of Khon Kaen University through Cholangiocarcinoma
Research Institute (CARI-BRF64-22), Office of the Permanent Secretary, Ministry of Higher Education, Science, Research
and Innovation (OPS MHESI), Thailand Science Research and Innovation (TSRI) and Khon Kaen University (Grant No. RGNS
64-051), and a grant from Khon Kaen University to A.J. (KKU62 Grant No. 6200010002).
Speakers
Apinya Jusakul