Human bile as a rich source of biomarkers for hepatopancreatobiliary cancers

Metabolic profiling of biofluids is emerging as an important area with a promising number of applications in clinical medicine, including early diagnosis of numerous diseases that normally remain silent until late in the progress of disease. While blood and urine are more often used to explore biomarkers that distinguish he healthy from disease conditions, human bile is emerging as a rich source of biomarkers specifically for the cancers of the liver (hepatocellular carcinoma), bile ducts (cholangiocarcinoma), gallbladder and pancreas. This is owing to the fact that metabolites linked to the pathways of tumor cell metabolism are rich in bile by virtue of its association or proximity to the pathological source. Recent methodological developments have enabled the identification of a number of bile metabolites that have links with hepatopancreatobiliary diseases. Investigations of human bile are also considered to help the biomarker discovery process in vitro and provide avenues for translational research in detecting and following dynamic variations of biomarkers in clinical settings using noninvasive approaches, such as in vivo magnetic resonance spectroscopy. This article reviews the current status and potential applications of human bile as a source of biomarkers, with emphasis on metabolites, for early detection of cancers associated with the hepatopancreatobiliary system.