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A Serum Metabolite Classifier for the Early Detection of Type 2 Diabetes Mellitus-Positive Hepatocellular Cancer.

ABSTRACT: Type 2 diabetes mellitus (T2DM) has been identified as an independent risk factor for hepatocellular cancer (HCC). However, there are no ideal biomarkers for the surveillance and early detection of HCC in the T2DM population at present. In this study, we aimed to explore novel metabolite biomarkers for T2DM-positive [T2DM(+)] HCC by metabolomic analysis. At first, many serum metabolites were found dysregulated in T2DM(+) HCC patients in untargeted metabolomic analyses. Targeted metabolite analyses confirmed that serum benzoic acid and citrulline were increased, and creatine was decreased in T2DM(+) HCC compared to the T2DM group. A metabolite classifier including benzoic acid, creatine, and citrulline was identified as a novel biomarker for the diagnosis of T2DM(+) HCC, with an area under the ROC curve (AUC) of 0.93 for discriminating T2DM(+) HCC patients from T2DM patients. In addition, the metabolite classifier detected small-size (AUC = 0.94), early-stage (AUC = 0.94), and AFP-negative (AUC = 0.96) tumors with high sensitivity and specificity. The combination of this metabolite classifier and AFP might be useful in the surveillance and early detection of HCC in the T2DM population. In conclusion, this study establishes a novel diagnostic tool for T2DM(+) HCC.

SUBMITTER: Cao LL

PROVIDER: S-EPMC9315765 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide. The lack of effective biomarkers for the early detection of HCC results in unsatisfactory curative treatments. Here, metabolite biomarkers were identified and validated for HCC diagnosis. A total of 1,448 subjects, including healthy controls and patients with chronic hepatitis B virus infection, liver cirrhosis, and HCC, were recruited from multiple centers in China. Liquid chromatography-mass spectrometry-based metabolomics methods were used to characterize the subjects' serum metabolic profiles and to screen and validate the HCC biomarkers. A serum metabolite biomarker panel including phenylalanyl-tryptophan and glycocholate was defined. This panel had a higher diagnostic performance than did α-fetoprotein (AFP) in differentiating HCC from a high-risk population of cirrhosis, such as an area under the receiver-operating characteristic curve of 0.930, 0.892, and 0.807 for the panel versus 0.657, 0.725, and 0.650 for AFP in the discovery set, test set, and cohort 1 of the validation set, respectively. In the nested case-control study, this panel had high sensitivity (range 80.0%-70.3%) to detect preclinical HCC, and its combination with AFP provided better risk prediction of preclinical HCC before clinical diagnosis. Besides, this panel showed a larger area under the receiver-operating characteristic curve than did AFP (0.866 versus 0.682) to distinguish small HCC, and 80.6% of the AFP false-negative patients with HCC were correctly diagnosed using this panel in the test set, which was corroborated by the validation set. The specificity and biological relevance of the identified biomarkers were further evaluated using sera from another two cancers and HCC tissue specimens, respectively. Conclusion: The discovered and validated serum metabolite biomarker panel exhibits good diagnostic performance for the early detection of HCC from at-risk populations. (Hepatology 2018;67:662-675).

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A Serum Metabolite Classifier for the Early Detection of Type 2 Diabetes Mellitus-Positive Hepatocellular Cancer.

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