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. 2024 Dec 6;10(24):e41008.
doi: 10.1016/j.heliyon.2024.e41008. eCollection 2024 Dec 30.

Biomarker potential of plasma cell-free DNA for cholangiocarcinoma

Sattrachai Prasopdee  1   2   3 , Sissades Tongsima  4 , Montinee Pholhelm  1   2   3 , Siraphatsorn Yusuk  1   2   3 , Sithichoke Tangphatsornruang  5 , Kritiya Butthongkomvong  6 , Teva Phanaksri  3 , Anthicha Kunjantarachot  3 , Jutharat Kulsantiwong  7 , Smarn Tesana  1   2 , Thanakrit Sathavornmanee  8 , Veerachai Thitapakorn  1   2   3
Affiliations

Biomarker potential of plasma cell-free DNA for cholangiocarcinoma

Sattrachai Prasopdee et al. Heliyon. .

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: Cell-free DNA; Cholangiocarcinoma; Circulating tumor DNA; Diagnosis; Opisthorchis viverrini; Ultra-low-pass whole-genome sequencing (ULP-WGS); iChorCNA.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Veerachai Thitapakorn reports financial support was provided by 10.13039/501100005790Thammasat University. Veerachai Thitapakorn reports a relationship with Thammasat University that includes: employment. The author declares, there is no conflict of interest for this study. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
The scatter plot of plasma cell-free DNA (cfDNA) concentration (A), percentage of tumor fraction (B), circulating tumor DNA (ctDNA) concentration (C), and average ploidy number (D). The plasma cell-free DNA (cfDNA) concentration, circulating tumor (ctDNA) concentration, percentage of tumor fraction, and average ploidy number is on the y-axis and group is on the x-axis. The green circle, the yellow square, and the pink triangle indicate the N, OV, and CCA respectively.
Fig. 2
Fig. 2
Bar chart of the plasma cfDNA concentration. The log plasma cfDNA concentration (ng/ml plasma) and group are plotted on the y- and x-axis, respectively. The error bars indicate the standard deviation of plasma cfDNA concentration. The asterisk (∗) indicates the statistical significance P < 0.05 of N vs CCA and OV vs CCA.
Fig. 3
Fig. 3
The AUC of the ROC curve of plasma cell-free DNA (cfDNA) concentration, circulating tumor DNA (ctDNA) concentration, tumor fraction. The % sensitivity is plotted against 100% - % specificity on the X-axis and Y-axis, respectively. The AUC of ROC curves and 95% CI are calculated and indicated in each curve.
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