The Search for Risk, Diagnostic and Prognostic Biomarkers of Cholangiocarcinoma and their Biological and Clinicopathological Significance

Cholangiocarcinomas (CCAs) are a heterogeneus group of malignant tumors that originate from the biliary tract. They are usually diagnosed in advanced stages, leading to a dismal prognosis for affected patients. As CCA often arises as a sporadic cancer in individuals lacking specific risk factors or with heterogeneous backgrounds, and there are no defined high-risk groups, the implementation of effective surveillance programs for CCA is problematic. The identification and validation of new biomarkers useful for risk stratification, diagnosis, prognosis and prediction of treatment response remains an unmet need for patients with CCA, even though numerous studies have been conducted lately to try to discover and validate CCA biomarkers. In this review, we overview the available information about the different types of biomarkers that have been investigated in recent years using minimally invasive biospecimens (blood, serum/plasma, bile, urine) and their potential usefulness in diagnosis, prognosis and risk stratification. It is widely accepted that early detection of CCA will impact patients' outcomes, by improving survival rates, quality of life, and the possibility of less invasive and/or curative treatments, however, challenges to its translation and clinical application for CCA patients need to be resolved.