Metabolomics in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, often arising on a background of chronic liver disease. Metabolomics—the comprehensive analysis of small-molecule metabolites—has emerged as a pivotal approach for unraveling the metabolic reprogramming that underlies tumour initiation, progression and therapeutic resistance. By profiling biofluids or tissue extracts through techniques such as mass spectrometry and nuclear magnetic resonance spectroscopy, researchers have characterised perturbations in glucose, lipid and amino acid pathways, as well as alterations in bile acid and acylcarnitine metabolism. These studies not only delineate the biochemical hallmarks of malignant transformation but also support the identification of diagnostic and prognostic biomarkers. Integration with complementary “omics” layers, including lipidomics and transcriptomics, further refines our understanding of tumour heterogeneity and microenvironmental interactions. Ultimately, metabolomic insights hold promise for early detection of HCC, stratification of patient risk and the development of metabolism-targeted therapies, thereby advancing personalised management of liver cancer.

Research from Nature Portfolio

A seminal serum metabolomics study used non-targeted gas chromatography–time of flight mass spectrometry and machine-learning analysis to map the metabolic trajectory from hepatitis B infection through cirrhosis to HCC. Fifteen metabolites linked to energy metabolism, macromolecular synthesis and redox balance were shown to discriminate successive disease stages with high accuracy. Key discriminators included phenylalanine, malic acid, palmitic acid, asparagine and β-glutamate, which collectively formed a metabolic panel capable of distinguishing early HCC from chronic liver injury. This work established a framework for metabolomics-based risk-stratification and early diagnostic strategies in hepatocarcinogenesis.

Metabolomics in Hepatocellular Carcinoma publication trend

The graph below shows the total number of articles in metabolomics in hepatocellular carcinoma across all publications each year (not limited to Nature Index journals).

Technical terms

Metabolomics: Systematic study of small-molecule metabolites within cells, tissues or biofluids.

Lipidomics: Subset of metabolomics focused on the comprehensive analysis of lipid species.

Untargeted metabolomics: Global profiling approach without predefined analyte selection.

Mass spectrometry imaging: Technique mapping the spatial distribution of metabolites in tissue sections.

Biomarker: Measurable indicator of a biological state or condition, often used for diagnosis or prognosis.

Acylcarnitine: Esterified carnitine molecules essential for transport of fatty acids into mitochondria for β-oxidation.

References

1. Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma. Scientific Reports (2015).
2. Integrated plasma metabolomics and lipidomics profiling highlights distinctive signature of hepatocellular carcinoma in HCV patients. Journal of Translational Medicine (2023).
3. Metabolic Reprogramming of HCC: A New Microenvironment for Immune Responses. International Journal of Molecular Sciences (2023).
4. Transcriptomic and metabolomic analyses reveal the spatial role of carnitine metabolism in the progression of hepatitis B virus cirrhosis to hepatocellular carcinoma. Frontiers in Microbiology (2024).