Identification of a novel plasma metabolite panel as diagnostic biomarker for hepatocellular carcinoma

Metabolic reprogramming is one of the hallmarks of cancer. Hepatocellular carcinoma (HCC) is one of the most lethal malignancy camcer, but the early diagnosis of HCC remains difficult. In this study, we searched for potential plasma metabolite biomarkers of HCC.A total of plasma samples of 104 HCC, 76 cirrhosis and 10 healthy subjects were assessed and validated through Gas chromatography-Mass spectrometry. Receiver-operating characteristic curves (ROC) combined with multivariate statistical analyses were used to assess the diagnostic performance of metabolites and combinations.10 metabolites in screening cohort were significantly changed in the plasma of HCC patients. Multivariate logistic regression analysis of candidate metabolites in validation cohort showed that N-formylglycine, oxoglutaric acid, citrulline and heptaethylene glycol could distinguish HCC from cirrhosis. The combination of these four metabolites showed a better performance than AFP with the Area Under the Curve (AUC), sensitivity, specificity as 0.940, 84.00%, 97.56%, respectively. In further, the panel of N-formylglycine, heptaethylene glycol and citrulline can more effectively discriminate early stage HCC from cirrhosis than AFP (AUC: 0.835 vs. 0.634). Finally, heptaethylene glycol could significantly inhibit the proliferation, migration and invasion of HCC cells in vitro.The combination of plasma N-formylglycine, oxoglutaric acid, citrulline, and heptaethylene glycol can be an efficient novel diagnostic biomarker for HCC.