Proteomic analysis of human bile reveals potential biomarkers for cholangiocarcinoma

Abstract

Degree Project Thesis, Programme in Medicine. TITLE: Proteomic analysis of human bile reveals potential biomarkers for cholangiocarcinoma. Background: Cholangiocarcinoma (CC), is the second most common primary liver cancer in most parts of the world. In western countries, primary sclerosing cholangitis (PSC) is one of the most common causes of CC. CC has a low survival rate, between 2-30% depending on type and spread, and diagnosis often comes late in the development of the tumor, due to a late clinical presentation and unsatisfactory diagnostic methods. It is particularly difficult to determine if biliary strictures in patients with PSC are benign or malignant in nature. In recent years, there has been an increased interest in the use of proteomic analysis of bile for the discovery of potential biomarkers to aid in the diagnosis of CC. Objective: The aim was to determine the existence of proteins whose relative abundance in bile differs depending on the underlying disease, in patients with biliary strictures. The main ambition was to discover one or more proteins with the ability to distinguish a benign biliary stricture from a malignant stricture in patients with PSC. Methods: Bile samples from 37 patients were analyzed in this prospective exploratory study, including 5 patients with de novo CC, 4 with CC and PSC, 7 with PSC only, 6 with pancreatic cancer, and 15 controls. The bile was aspirated from patients undergoing endoscopic retrograde cholangiopancreatography. For one sample, bile was aspirated by percutaneous transhepatic cholangiography. Nano liquid chromatography tandem mass spectrometry was used for mass analysis. Proteins were identified by searches against a public database of human peptide sequences. Lastly, SPSS Statistical Package was used to calculate if there was a statistically significant difference in abundance of proteins between patient groups. Results: A total of 6 proteins were identified where the relative abundance differed significantly between patient groups (p < 0.05). The most promising finding was that the known tumor suppressor Receptor-type tyrosine-protein phosphatase eta (R-PTP-eta) was less abundant in patients with CC than in the control population and patients with PSC only. Conclusions: The differential abundance of certain proteins present in human bile, such as RPTP- eta, can be used to differentiate CC from other diseases of the bile ducts. None of the proteins described in this study were alone able to distinguish a benign biliary stricture from a malignant stricture in patients with PSC. Further studies are warranted to examine the usefulness of these proteins as clinical tumor markers for CC