Alterations in serum metabolic profiles of early-stage hepatocellular carcinoma patients after radiofrequency ablation therapy.

ABSTRACT

OBJECTIVE: To investigate the alterations in serum metabolic profiles and early-stage hepatocellular carcinoma (HCC) patient characteristics after radiofrequency ablation (RFA) therapy. This evaluation aimed to assess treatment effectiveness and identify potential novel approaches and targets for HCC treatment and prognosis monitoring. METHODS: Untargeted metabolomics technology was employed to analyze serum metabolic profiles in healthy volunteer controls (NCs) and early stage HCC patients before and after RFA therapy. Additionally, Human Metabolome Database and Kyoto Encyclopedia of Genes and Genomes database were used to identify the differential metabolites (DMs) and metabolic pathways. Cystoscape was utilized to construct DM gene networks. Amino acid analyses were performed to validate our findings. RESULTS: We identified 11, 14, and six DMs between the NC and HCC groups, HCC patients before and after RFA therapy, and post-RFA HCC and NC groups, respectively. The expression levels of these DMs, particularly those of amino acids and lipids, significantly changed. Compared with the NC group, higher levels of L-tyrosine, aspartate, and 18-oxo-oleate were observed in HCC patients, which were significantly reduced in patients after RFA therapy. Meanwhile, HCC patients after RFA therapy had increased levels of L-arginine, phosphatidic acid (203), and lysophosphatidyl choline (LPC) (204) compared to those before therapy, while their levels before therapy were lower than those of NC. Moreover, most metabolites in the post-RFA and NC groups showed no significant changes in expression, except for L-tyrosine and LPC (160). These metabolites could potentially serve as characteristic factors of early-stage HCC patients after RFA therapy. Joint pathway analysis revealed striking changes, mainly in phenylalanine, tyrosine, and tryptophan biosynthesis; alanine, aspartate, and glutamate metabolism; and arginine and aminoacyl-tRNA biosynthesis. Bioinformatics analysis of publicly available data preliminarily identified 187 DM-related metabolic enzymes. CONCLUSION: Our study proposed novel targets for early-stage HCC treatment, laying the groundwork for improving treatment efficacy and prognosis of early-stage HCC patients.