Exhaled volatile organic compounds for cholangiocarcinoma diagnosis

Objectives: The difficulties in the early detection consequent to the lack of sensitive biomarkers render patients with cholangiocarcinoma (CCA) to have poor outcomes. Recently, sensitive and specific volatile organic compounds (VOCs) were identified in several cancers. However, the VOC profiles in CCA are not well-studied. Thus, we investigated the VOC profiles in exhaled breath of CCA patients and controls. Methods: We prospectively collected exhaled breath samples from 30 consecutive patients newly diagnosed with CCA and 30 controls who did not have CCA (seven had benign biliary strictures and 23 had other medical conditions). Exhaled VOCs were identified using gas chromatography mass spectrometry Triple Quadrupoles system. Analysis of the significant differences in VOCs between cases and controls was conducted using supervised multivariate regression analysis. Further validation was performed for these VOCs in another cohort of 18 CCA patients and 22 controls. Results: Levels of six compounds were significantly different between CCA patients and controls, namely, acetone, isopropyl alcohol, dimethyl sulfide, 1,4-pentadiene, allyl methyl sulfide, and N,N-dimethylacetamide. Acetone and dimethyl sulfide were independently associated with CCA as demonstrated in the multivariate analysis. Using the cut-off value of 8.59 × 107 arbitrary unit (AU), acetone had a sensitivity and specificity of 82.1% and 75.8%, respectively, with an area under the receiving operator curve (AUROC) of 0.85 for the CCA diagnosis. Acetone level was also significantly different between cases and controls in the validation cohort. Using the same cut-off value, the sensitivity, specificity, and AUROC was 59.1%, 66.7%, and 0.85, respectively. Conclusion: Breath analysis may potentially be useful for CCA diagnosis. A cohort of patients with early-stage CCA in further studies is needed to confirm the ability of exhaled VOCs for the early detection of CCA.