Biomarker potential of plasma cell-free DNA for cholangiocarcinoma

• Published in: Heliyon Vol. 10; no. 24; p. e41008
• Main Authors: Prasopdee, Sattrachai, Tongsima, Sissades, Pholhelm, Montinee, Yusuk, Siraphatsorn, Tangphatsornruang, Sithichoke, Butthongkomvong, Kritiya, Phanaksri, Teva, Kunjantarachot, Anthicha, Kulsantiwong, Jutharat, Tesana, Smarn, Sathavornmanee, Thanakrit, Thitapakorn, Veerachai
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 30.12.2024; Elsevier
• Subjects: biomarkers; Cell-free DNA; Cholangiocarcinoma; Circulating tumor DNA; Diagnosis; DNA; fluorometry; iChorCNA; neoplasms; odds ratio; opisthorchiasis; Opisthorchis viverrini; ploidy; Ultra-low-pass whole-genome sequencing (ULP-WGS); iChorCNA; Cell-free DNA; Ultra-low-pass whole-genome sequencing (ULP-WGS); Diagnosis; Opisthorchis viverrini; Circulating tumor DNA; Cholangiocarcinoma
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e41008

To prevent the development of cholangiocarcinoma, an effective screening opisthorchiasis viverrini and/or differential diagnosis of and the cholangiocarcinoma is crucial needed. The level and quality of cfDNA in plasma are being investigated for their potential role as biomarkers in cholangiocarcinoma. The study enrolled 43 healthy controls (N), 36 O. viverrini-infected subjects (OV), and 36 cholangiocarcinoma patients (CCA). Plasma cfDNA was quantified by fluorometry (Qubit 4), and qualified analysis, including % tumor fraction, ctDNA, ploidy number, and somatic copy number alteration (SCNA), was conducted using ULP-WGS and analyzed by iChorCNA. The statistical analysis and comparison among the groups were performed. The results showed that cfDNA could effectively differentiate between N and OV from CCA statistically both by DNA amount and quality. Using a cut-off of >20.94 ng/ml, the sensitivity and specificity of the cfDNA concentration were determined to be 86.11% and 98.73% for the differential diagnosis of cholangiocarcinoma, respectively. The ULP-WGS with iChorCNA indicated the % tumor fraction of cfDNA (P < 0.001) and the values of the ploidy number (P < 0.001) of the cholangiocarcinoma group and the other groups were statistically significant. Moreover, the SCNA of the cholangiocarcinoma group was shown to be significantly high in comparison to that of the healthy control group with an odds ratio of 11.688 (P < 0.001). The use of cfDNA concentration and ULP-WGS for analyzing DNA quality including % tumor fraction, ctDNA concentration, tumor ploidy, and SCNA are useful for the differential diagnosis of cholangiocarcinoma from opisthorchiasis viverrini and healthy individuals. [Display omitted] •These findings investigated both quantitative and qualitative detection of plasma cell-free DNA in a cost-effective manner which allowing patients to access the test and potentially prevent the development of cholangiocarcinoma.•ULP-WGS determined the SCNA in cholangiocarcinoma, revealing a pattern of chromosome 6 loss which belong the HLA locus.•The 94.44 % sensitivity and 100 % specificity were obtained when using a cut-off of >19.78 ng/ml for cfDNA concentration.