Urinary metabolic profiling identifies a key role for glycocholic acid in human liver cancer by ultra-performance liquid-chromatography coupled with high-definition mass spectrometry

BackgroundMetabolomics has been proposed to be a hallmark of cancer, yet a systematic characterization of a metabolite and metabolic pathways in human hepatocarcinoma (HCC) remains a challenge.MethodsUsing ultra-performance liquid-chromatography/quadrupole-time-of-flight coupled with high-definition mass spectrometry (UPLC–Q-TOF–HDMS) in conjunction with multivariate data analysis methods, we identified and measured the metabolite profile of glycocholic acid from urine samples obtained from patients with HCC diseases. Bioinformatic tools were used to construct the metabolite network that can identify a key role for glycocholic acid in HCC.ResultsBiochemical analyses revealed that glycocholic acid expression was up-regulated in urine samples associated with HCC. Its pathway analysis suggested the modulation of multiple vital physiological pathways, including primary bile acid biosynthesis, secondary bile acid biosynthesis, metabolic pathways, and bile secretion. The network generation clearly enhances the interpretation and understanding of mechanisms for glycocholic acid.ConclusionsMetabolomics can contribute to evaluating the potential of metabolites in HCC patients and may provide new insight into pathophysiologic mechanisms.

► Urine metabolomics provides a powerful platform for discovering novel biomarkers.
► Glycocholic acid was separated and identified by UPLC–Q-TOF–HDMS tool.
► Pathway analysis for better understanding of the metabolites networks in biological context.
► Metabolite networks clearly enhance the understanding on mechanisms of glycocholic acid.
► Robust urine metabonomics provides new insight into pathophysiologic mechanisms.