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

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.