Proteome analysis of biliary extracellular vesicles by high-precision mass spectrometry reveals potential biomarkers for cholangiocarcinoma and primary sclerosing cholangitis
Abstract
Background Patients with primary sclerosing cholangitis (PSC) are at high risk of developing biliary cancer. Sufficient diagnostics do not yet exist to detect early cholangiocarcinoma (CCA). This study aimed to explore biomarkers in extracellular vesicles (EVs) in the bile of patients with CCA and PSC. Methods 90 bile samples from 30 patients with CCA, PSC and bile stone were included retrospectively. Vesicles were enriched via differential centrifugation and filtering. EV characterization was performed via electron microscopy and Western blotting for EV markers. Particle concentration was measured via nanoparticle tracking analysis (NTA). Pooled samples were analyzed by liquid chromatography‒mass spectrometry (LC‒MS). Data analysis was carried out via MaxQuant and R. Results The EV pellets of CCA samples contained the largest number of proteins. After quantile normalization and t-testing with an adjusted p-value (FDR)
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