Dataset Information

Molecular and Metabolic Phenotyping of Hepatocellular Carcinoma for Biomarker Discovery: A Meta-Analysis.

ABSTRACT: Identifying and translating hepatocellular carcinoma (HCC) biomarkers from bench to bedside using mass spectrometry-based metabolomics and lipidomics is hampered by inconsistent findings. Here, we investigated HCC at systemic and metabolism-centric multiomics levels by conducting a meta-analysis of quantitative evidence from 68 cohorts. Blood transcript biomarkers linked to the HCC metabolic phenotype were externally validated and prioritized. In the studies under investigation, about 600 metabolites were reported as putative HCC-associated biomarkers; 39, 20, and 10 metabolites and 52, 12, and 12 lipids were reported in three or more studies in HCC vs. Control, HCC vs. liver cirrhosis (LC), and LC vs. Control groups, respectively. Amino acids, fatty acids (increased 18:1), bile acids, and lysophosphatidylcholine were the most frequently reported biomarkers in HCC. BAX and RAC1 showed a good correlation and were associated with poor prognosis. Our study proposes robust HCC biomarkers across diverse cohorts using a data-driven knowledge-based approach that is versatile and affordable for studying other diseases.

SUBMITTER: Anh NH

PROVIDER: S-EPMC10672761 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Molecular and Metabolic Phenotyping of Hepatocellular Carcinoma for Biomarker Discovery: A Meta-Analysis.

Anh Nguyen Hoang NH Long Nguyen Phuoc NP Min Young Jin YJ Ki Yujin Y Kim Sun Jo SJ Jung Cheol Woon CW Park Seongoh S Kwon Sung Won SW Lee Seul Ji SJ

Metabolites 20231027 11

Identifying and translating hepatocellular carcinoma (HCC) biomarkers from bench to bedside using mass spectrometry-based metabolomics and lipidomics is hampered by inconsistent findings. Here, we investigated HCC at systemic and metabolism-centric multiomics levels by conducting a meta-analysis of quantitative evidence from 68 cohorts. Blood transcript biomarkers linked to the HCC metabolic phenotype were externally validated and prioritized. In the studies under investigation, about 600 metabo ...[more]

PMID: 37999208

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Project description:Chronic hepatic disease damages the liver, and the resulting wound-healing process leads to liver fibrosis and the subsequent development of cirrhosis. The leading cause of hepatic fibrosis and cirrhosis is infection with hepatitis C virus (HCV), and of the patients with HCV-induced cirrhosis, 2% to 5% develop hepatocellular carcinoma (HCC), with a survival rate of 7%. HCC is one of the leading causes of cancer-related death worldwide, and the poor survival rate is largely due to late-stage diagnosis, which makes successful intervention difficult, if not impossible. The lack of sensitive and specific diagnostic tools and the urgent need for early-stage diagnosis prompted us to discover new candidate biomarkers for HCV and HCC. We used aptamer-based fractionation technology to reduce serum complexity, differentially labeled samples (six HCV and six HCC) with fluorescent dyes, and resolved proteins in pairwise two-dimensional difference gel electrophoresis. DeCyder software was used to identify differentially expressed proteins and spots picked, and MALDI-MS/MS was used to determine that ApoA1 was down-regulated by 22% (p < 0.004) in HCC relative to HCV. Differential expression quantified via two-dimensional difference gel electrophoresis was confirmed by means of (18)O/(16)O stable isotope differential labeling with LC-MS/MS zoom scans. Technically independent confirmation was demonstrated by triple quadrupole LC-MS/MS selected reaction monitoring (SRM) assays with three peptides specific to human ApoA1 (DLATVYVDVLK, WQEEMELYR, and VSFLSALEEYTK) using (18)O/(16)O-labeled samples and further verified with AQUA peptides as internal standards for quantification. In 50 patient samples (24 HCV and 26 HCC), all three SRM assays yielded highly similar differential expression of ApoA1 in HCC and HCV patients. These results validated the SRM assays, which were independently confirmed by Western blotting. Thus, ApoA1 is a candidate member of an SRM biomarker panel for early diagnosis, prognosis, and monitoring of HCC. Future multiplexing of SRM assays for other candidate biomarkers is envisioned to develop a biomarker panel for subsequent verification and validation studies.

Dataset Information

Molecular and Metabolic Phenotyping of Hepatocellular Carcinoma for Biomarker Discovery: A Meta-Analysis.

Publications

Molecular and Metabolic Phenotyping of Hepatocellular Carcinoma for Biomarker Discovery: A Meta-Analysis.

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