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Non-invasive biomarkers to improve early diagnosis of hepatic diseases

Researchers at Biodonostia Health Research Institute, coordinated by Ikerbasque researcher Jesús Bañales, recently published the results of an international collaborative study, in which they describe new non-invasive biomarkers for diagnosing cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC) and primary sclerosing cholangitis (PSC).

This work, recently published in the prestigious Hepatology journal, concludes that extracellular vesicles in the blood contain sensitive and specific protein biomarkers with diagnostic capacity for these diseases. “The biomarkers found may hold enormous value for the diagnosis of these pathologies using non-invasive methods, and for their capacity of differential diagnosis”, explained Jesús Bañales, the researcher coordinating the study and also head of the Hepatic Diseases group in the Biodonostia HRI hepatic and gastrointestinal area directed by Luis Bujanda (CIBERehd, University of the Basque Country Researcher and doctor specialising in the Digestion at the Donostialdea IHO).

In recent years, the extracellular vesicles present in different biological fluids have become an important tool in the search for biomarkers for different disorders, and for factors involved in the development and evolution of diseases.

This study had the participation of 134 patients with cholangiocarcinoma, primary sclerosing cholangitis and hepatocellular carcinoma, including controls of healthy individuals from the Donostia University Hospital, Cruces University Hospital and the Hospital Varsovia. Infrastructures and equipment from CIC Biogune (proteomic platform and Exosomes Laboratory) were also made available to analyse the samples. The proteomic profiles revealed multiple proteins expressed in differential manner among the different groups, showing strong potential as diagnostic tools for these diseases.

Based on the positive data obtained from this study, and within the Strategic Action financed by the AECC (Spanish Association Against Cancer), in the coming years the international validation of said biomarkers will be implemented in order to finally establish their clinical value.

Primary sclerosing cholangitis (PSC) is a progressive inflammatory disease of the bile ducts, autoimmune in origin, characterised by inflammation with progressive fibrosis and narrowing of the biliary tract inside and outside the liver and which can lead to the appearance of cirrhosis, hepatic insufficiency and sometimes cancer of the biliary tract.  Cholangiocarcinoma (CCA) or bile duct cancer is an uncommon but highly aggressive type of tumour which is difficult to diagnose at the early stages. For its part, hepatocellular carcinoma (HCC) is the primary, most frequent liver tumour (constituting 90% of cases) and has a high death rate.

Although these are three different pathologies, in the majority of cases the tumours are diagnosed at advanced stages of the disease, meaning that in all of them early and differentiated diagnosis is essential in establishing the most appropriate therapeutic strategy in each case.

Reference: Arbelaiz, A., Azkargorta, M., Krawczyk, M., Santos-Laso, A., Lapitz, A., Perugorria, M. J., Erice, O., Gonzalez, E., Jimenez-Agüero, R., Lacasta, A., Ibarra, C., Sanchez-Campos, A., Jimeno, J. P., Lammert, F., Milkiewicz, P., Marzioni, M., Macias, R. I.R., Marin, J. J.G., Patel, T., Gores, G. J., Martinez, I., Elortza, F., Falcon-Perez, J. M., Bujanda, L. and Banales, J. M. (2017), Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma. Hepatology, 66: 1125–1143. doi:10.1002/hep.29291