Metabolomic biomarkers for hepatocellular carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is a highly malignant cancer which lack of effective diagnosis and prognosis biomarkers, therefore surging studies focused on the metabolite candidates for HCC. The current study was designed to systematically review the metabolic studies for HCC, summarize the current available evidence and provide implication for further studies within this area. By systematically screening Pubmed and Embase, and eligibility assessment, we eventually included 55 pieces of studies. After summarized their characteristics, we reviewed them by 3 parts, regarding to the different biofluid they carried out the experiments. By collecting the candidates from all the included studies, we carried out pathway enrichment to see the representative of the reported candidates, as expected the pathway consistent with the current knowledge of HCC. Next, we conduct quality assessment on the included studies. Only 36% of the current evidence grouped as high quality, indicating the quality of metabolic studies needs further improvement.

Comprehensive Multi-Omic Analysis Reveals Distinct Molecular Features in Early and Advanced Stages of Hepatocellular Carcinoma

“…Although phosphopeptides, ordinary tryptic peptides, metabolites, and lipids are all detected by LC-MS/MS, at a practical level, phosphoproteomics is considerably more complex and challenging to implement for clinical samples than other omics. Previous studies have identified over 20,000 phosphopeptides or phosphorylation sites in HCC tumors using high-pH reverse phase fractionation (one sample, six injections) and TiO2 enrichment [23][24][25][26][27][28][29][30][31][32][33][34]. Taking advantage of the high sensitivity and speed of the timsTOF Pro 2 mass spectrometer and the complementary results of IMAC Fe-NTA and TiO2 profiling [45][46][47], a comparable number of phosphopeptides has been obtained using a much simpler approach (one sample, two injections; routine DDA data acquisition without projectspecific proteomics libraries).…”

“…Previous studies have shown that metabolic molecules involved in glycolysis, the TCA cycle, amino acid metabolism, and bile acid metabolism are disrupted in association with HCC [31][32][33]. Lipidomics is a complementary approach to metabolomics that primarily profiles endogenous hydrophobic compounds.…”

Prediagnostic plasma metabolite concentrations and liver cancer risk: a population-based study of Chinese men

“… 10 , 11 , 12 , 13 , 14 Several metabolites and biochemical pathways have been identified, such as bile acid biosynthesis, biosynthesis of amino acids and proteins, lipid metabolism, etc. 15 , 16 However, the majority of existing studies, conducted in hospital settings and including prevalent patients with cancer, may be susceptible to reverse causation. Additionally, these studies often have relatively small sample sizes, potentially compromising their power to detect weak associations.…”

Biomarker Discovery for Hepatocellular Carcinoma in Patients with Liver Cirrhosis Using Untargeted Metabolomics and Lipidomics Studies

“…Among these, metabolomics and lipidomics approaches were employed to analyze various categories of biological samples using manifold liquid/gas chromatography-mass spectrometry and nuclear magnetic resonance (NMR) systems. Multiple research groups have reported various classes of metabolites, including amino acids, organic acids, bile acids, fatty acids, and lipids, as potential biomarkers for the diagnosis of HCC [12][13][14][15]. However, the efficacy of the identified biomarkers in distinguishing early HCC from LC remains to be evaluated, which is the most difficult aspect of HCC diagnosis.…”