Cancers, 2019. 11(10), 0-, DOI: https://doi.org/10.3390/cancers11101497

Comprehensive Metabolomic Search for Biomarkers to Differentiate Early Stage Hepatocellular Carcinoma from Cirrhosis

Da Jung Kim, Eun Ju Cho;Kyung-Sang Yu;In-Jin Jang;Jung-Hwan Yoon;Taesung Park;Joo-Youn Cho

Abstract

The established biomarker for hepatocellular carcinoma (HCC), serum α-fetoprotein(AFP), has suboptimal performance in early disease stages. This study aimed to develop ametabolite panel to differentiate early-stage HCC from cirrhosis. Cross-sectional metabolomicanalyses of serum samples were performed for 53 and 47 patients with early HCC and cirrhosis,respectively, and 50 matched healthy controls. Results were validated in 82 and 80 patients withearly HCC and cirrhosis, respectively. To retain a broad spectrum of metabolites, technically distinctanalyses (global metabolomic profiling using gas chromatography time-of-flight mass spectrometryand targeted analyses using liquid chromatography with tandem mass spectrometry) wereemployed. Multivariate analyses classified distinct metabolites; logistic regression was employed toconstruct a prediction model for HCC diagnosis. Five metabolites (methionine, proline, ornithine,pimelylcarnitine, and octanoylcarnitine) were selected in a panel. The panel distinguished HCCfrom cirrhosis and normal controls, with an area under the receiver operating curve (AUC) of 0.82;this was significantly better than that of AFP (AUC: 0.75). During validation, the paneldemonstrated significantly better predictability (AUC: 0.94) than did AFP (AUC: 0.78). Defects inammonia recycling, the urea cycle, and amino acid metabolism, demonstrated on enrichmentpathway analysis, may reliably distinguish HCC from cirrhosis. Compared with AFP alone, themetabolite panel substantially improved early-stage HCC detection.

• DOI: https://doi.org/10.3390/cancers11101497
• ISBN or ISSN: 2072-6694

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.