Novel approaches in search for biomarkers of cholangiocarcinoma

Abstract

Cholangiocarcinoma (CCA) arises from the ductular epithelium of the biliary tree, either within the liver (intrahepatic CCA) or more commonly from the extrahepatic bile ducts (extrahepatic CCA). This disease has a poor prognosis and a growing worldwide prevalence. The poor outcomes of CCA are partially explained by the fact that a final diagnosis is challenging, especially the differential diagnosis between hepatocellular carcinoma and intrahepatic CCA, or distal CCA and pancreatic head adenocarcinoma. Most patients present with an advanced disease, unresectable disease, and there is a lack in non-surgical therapeutic modalities. Not least, there is an acute lack of prognostic biomarkers which further complicates disease management. Therefore, there is a dire need to find alternative diagnostic and follow-up pathways that can lead to an accurate result, either singlehandedly or combined with other methods. In the "-omics" era, this goal can be attained by various means, as it has been successfully demonstrated in other primary tumors. Numerous variants can reach a biomarker status ranging from circulating nucleic acids to proteins, metabolites, extracellular vesicles, and ultimately circulating tumor cells. However, given the relatively heterogeneous data, extracting clinical meaning from the inconsequential noise might become a tall task. The current review aims to navigate the nascent waters of the non-invasive approach to CCA and provide an evidence-based input to aid clinical decisions and provide grounds for future research.

Keywords: Cholangiocarcinoma, Biomarker, Proteomics, Metabolomics, Extracellular vesicles, Circulating nucleic acids

Core Tip: The current review paper aims to critically analyze the most recent developments in non-invasive cholangiocarcinoma diagnosis and prognosis. The article takes an in-depth look at the fields of circulating nucleic acids, proteomic and metabolomic-derived biomarkers, extracellular vesicles, and circulating tumor cells in an attempt to outline promising results for future research and clinical use.