PO-091 Droplet digital PCR based detection of aberrantly methylated genes in bile identifies cholangiocarcinoma in patients with primary sclerosing cholangitis

Abstract

IntroductionPatients with primary sclerosing cholangitis (PSC) have up to 20% lifetime risk of developing cholangiocarcinomas (CCAs). Identifying CCA in patients with PSC is, however, complicated and current strategies are suffering from low sensitivity. Consequently, the majority of patients are diagnosed at an advanced, incurable stage of disease, highlighting the need for novel detection methods, which could qualify more patients for curative treatment. In the current study, we aimed at establishing a robust DNA methylation biomarker panel in bile for improved detection of CCA.Material and methodsMore than 300 bile samples (100 µl) from patients with PSC, CCA with and without PSC, and other non-malignant liver diseases were collected during endoscopic retrograde cholangiopancreatography or liver transplantation. All samples were analysed for promoter methylation of selected markers, using highly sensitive droplet digital PCR (ddPCR). In each reaction, an in-house 4-marker control assay was included for normalisation, and an algorithm for automated threshold determination, PoDCall, was applied for increased precision (Pharo et al, Clinical Epigenetics 2018).Results and discussionsPreliminary results indicate that the DNA methylation biomarkers have high accuracy for identifying CCA, particularly among patients with PSC. Interestingly, the markers were able to detect 5/8 PSC patients that later developed CCA, and that were not detected by standard diagnostic tools.ConclusionBy using highly sensitive ddPCR based technology and a robust DNA methylation biomarker panel, CCA can be accurately detected in small volumes of bile from patients with PSC.