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Plasma metabolomic profiling for hepatocellular carcinoma diagnosis and microvascular invasion prediction

ABSTRACT: Altered metabolites play a crucial role in the development and progression of hepatocellular carcinoma (HCC). In this study, an untargeted metabolomic analysis was conducted to identify novel biomarkers with high sensitivity and specificity for the early detection of HCC and to explore their functions. Plasma samples were collected from 138 HCC patients, 69 patients with benign hepatic lesions, and 35 healthy donors. These samples were divided into a discovery set of 171 and a validation set of 71, and analyzed using ultra high performance liquid chromatography mass spectrometry. Through paired t-tests and orthogonal partial least-squares discriminant analysis, nine metabolites with significant predictive value were selected out and incorporated into a model for HCC diagnosis. Area under curves for the discovery set, the validation set, and all samples were 0.97, 0.95, and 0.96 respectively. The satisfactory diagnostic performance was maintained regardless of the China liver cancer (CNLC) staging. Additionally, this model demonstrated better diagnostic performance than AFP when comparing HCC to controls in different CNLC stages. The metabolite pathway enrichment analysis showed that alterations in plasma bile acids were associated with cirrhosis. Univariate and multivariate analyses indicated that the ratio of L-Serine and Sarcosine was an independent predictor for MVI. An integrated analysis of metabolomic data with transcriptomic data from the Cancer Genome Atlas revealed that the low expression of AGXT and GATM was more likely related to MVI. To sum up, our research findings may offer valuable insights into HCC metabolic alterations and contribute to a better characterization of HCC.

INSTRUMENT(S): Liquid Chromatography MS - positive - hilic, Liquid Chromatography MS - negative - hilic

PROVIDER: MTBLS11996 | MetaboLights | 2025-07-02

REPOSITORIES: MetaboLights

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Project description:In cancer management, early and accurate diagnosis of hepatocellular carcinoma (HCC) is important for enhancing survival rate of patients. Currently, serum alpha-fetoprotein (AFP) is the only one biomarker for detection of HCC. However, serum AFP is not satisfactory for diagnosis of HCC due to its low accuracy (about 60-70%). In this study, we collected 109 serum samples (discovery set) from healthy control (HC) and patients with chronic hepatitis B (CHB), liver cirrhosis (LC) and HCC, and analyzed them with custom lncRNA microarray. Profiling analysis shows 181 differentially expressed lncRNAs between HCs and patients with CHB, LC and HCC. Then a 48-lncRNA diagnostic signature was identified with 100% predictive accuracy for all subjects in the discovery set. This diagnostic signature was verified with a cross-validation analysis in the discovery set. To further corroborate the signature, we gathered another 66 serum samples (validation set) and also analyzed them with microarray. The result indicates that the same signature has similar diagnostic accuracy for HC (100%), CHB (73%), LC (88%) and HCC (95%), implying a reproducible diagnostic biomarker for HCC. Receiver operating characteristic (ROC) analysis exhibits that this signature has significantly higher diagnostic accuracy for HCC and non-cancerous subjects (area under curve [AUC]: 0.994) than AFP (AUC: 0.773) in the discovery set and this was also verified in the validation set (0.964 vs 0.792). More importantly, the signature detected small HCC (<3cm) with 100% (13/13) accuracy while AFP with only 61.5% (8/13). Altogether, this study demonstrates that the serum 48-lncRNA signature is not only a powerful and sensitive biomarker for diagnosis of HCC but also a potential biomarker for LC. ***************************************************************** Submitter declares these data are subject to patent number ZL 2016 1 0397094. *****************************************************************

			Action	DRS
	HC1.mzXML	Mzxml
	HC10.mzXML	Mzxml
	HC11.mzXML	Mzxml
	HC12.mzXML	Mzxml
	HC13.mzXML	Mzxml

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Plasma metabolomic profiling for hepatocellular carcinoma diagnosis and microvascular invasion prediction

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