Abstract
Background and AimsBile analysis has the potential to serve as a surrogate marker for inflammatory and neoplastic disorders of the biliary epithelium and may provide insight into biliary pathophysiology and possible diagnostic markers. We aimed to identify biliary protein markers of patients with primary sclerosing cholangitis (PSC) by a proteomic approach.MethodsBile duct-derived bile samples were collected from PSC patients (n = 45) or patients with choledocholithiasis (n = 24, the control group). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to analyse the proteins, 2-D-gel patterns were compared by densitometry, and brush cytology specimens were analysed by RT-PCR.ResultsA reference bile-duct bile proteome was established in the control group without signs of inflammation or maligancy comprising a total of 379 non-redundant biliary proteins; 21% were of unknown function and 24% had been previously described in serum. In PSC patients, the biliary S100A9 expression was elevated 95-fold (p<0.005), serum protein expression was decreased, and pancreatic enzyme expression was unchanged compared to controls. The S100A9 expression was 2-fold higher in PSC patients with high disease activity than in those with low activity (p<0.05). The brush cytology specimens from the PSC patients with high disease activity showed marked inflammatory activity and leukocyte infiltration compared to the patients with low activity, which correlated with S100A9 mRNA expression (p<0.05).ConclusionsThe bile-duct bile proteome is complex and its analysis might enhance the understanding of cholestatic liver disease. Biliary S100A9 levels may be a useful marker for PSC activity, and its implication in inflammation and carcinogenesis warrants further investigation.
Highlights
Cholestatic liver disease (CLD) is a major cause of liver damage and failure
CLD pathogenesis ranges from choledocholithiasis, which is often completely relieved by endoscopic intervention, to chronic diseases such as primary sclerosing cholangitis (PSC), which may require liver transplantation [1,2,3] [4]
We focused on PSC, with the goals of gaining new insights into CLD pathophysiology and establishing a strong basis for the discovery of new diagnostic markers
Summary
Cholestatic liver disease (CLD) is a major cause of liver damage and failure. CLD pathogenesis ranges from choledocholithiasis, which is often completely relieved by endoscopic intervention, to chronic diseases such as primary sclerosing cholangitis (PSC), which may require liver transplantation [1,2,3] [4]. For some CLD pathologies (e.g., transporter defects), the underlying pathological mechanisms have been thoroughly elucidated, whereas for others, including PSC and post-transplant cholangiopathies, the pathophysiological basis of the disease and disease progression remain much less clear [5]. Some forms of CLD are complicated by malignancy, cholangiocarcinomas. We aimed to identify biliary protein markers of patients with primary sclerosing cholangitis (PSC) by a proteomic approach
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