Abstract
Hepatitis C virus (HCV) infection is associated with a high risk of developing hepatocellular carcinoma (HCC) and HCC recurrence remains the primary threat to outcomes after curative therapy. In this study, we compared recurrent and non-recurrent HCC patients treated with radiofrequency ablation (RFA) in order to identify characteristic metabolic profile variations associated with HCC recurrence. Gas chromatography-mass spectrometry (GC-MS) -based metabolomic analyses were conducted on serum samples obtained before and after RFA therapy. Significant variations were observed in metabolites in the glycerolipid, tricarboxylic acid (TCA) cycle, fatty acid, and amino acid pathways between recurrent and non-recurrent patients. Observed differences in metabolites associated with recurrence did not coincide before and after treatment except for fatty acids. Based on the comparison of serum metabolomes between recurrent and non-recurrent patients, key discriminatory metabolites were defined by a random forest (RF) test. Two combinations of these metabolites before and after RFA treatment showed outstanding performance in predicting HCV-related HCC recurrence, they were further confirmed by an external validation set. Our study showed that the determined combination of metabolites may be potential biomarkers for the prediction of HCC recurrence before and after RFA treatment.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world [1]
Hepatitis C virus (HCV) infection is associated with a high risk of developing hepatocellular carcinoma (HCC) and HCC recurrence remains the primary threat to outcomes after curative therapy
We have investigated dynamic metabolic serum changes, before and after radiofrequency ablation (RFA) for HCC, taking into account the presence of subsequent recurrence
Summary
Despite improvements in survival rates in recent years [2, 3], its worldwide incidence and malignancy-associated death rates are still challenging due to high rates of recurrence and difficulties associated with prognosis assessment. Radiofrequency ablation (RFA) is preferred when HCC is diagnosed at an early stage or when the tumor size is small. This approach has demonstrated safety and relative simplicity, and creates a minimal operative wound for patients [4]. The worldwide prevalence of hepatitis C-related HCC has been increasing in recent years. In countries such as Japan, Egypt, and some African countries, hepatitis C virus (HCV) infection is the primary cause of HCC [5]. HCC may be induced indirectly via HCV-associated chronic inflammation, cell death, proliferation, and cirrhosis [7]
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