Integrated serum proteomics and metabolomics reveal an INR-associated multi-omics signature in hepatocellular carcinoma.

backgroundCoagulation dysfunction is a common complication of hepatocellular carcinoma (HCC) and is reflected clinically by the international normalized ratio (INR), yet its serum molecular correlates remain poorly defined. We aimed to identify an INR-associated serum multi-omics signature in HCC and characterize the underlying molecular networks.

methodsWe performed serum proteomics and untargeted metabolomics on 52 HCC patients and 30 healthy controls. HCC patients were stratified by INR levels. Differential molecules were integrated using pathway analysis. LASSO and logistic regression were used to derive an INR-associated multi-omics signature.

resultsProteomics and metabolomics identified 1,810 DEPs and 246 DEMs between HCC and controls. Integrated analysis mapped these changes to 101 shared pathways, highlighting cholesterol and central carbon metabolism. LASSO selected an eight-molecule signature comprising four proteins (CAMK2B, TGFB1, IDH1, LDHA) and four metabolites (DL-tryptophan, ornithine, D-glutamine, lysine) that discriminated INR-defined coagulation abnormality (AUC 0.859). WGCNA indicated remodeling of the coagulation-complement axis. In the TCGA-LIHC cohort, core genes were dysregulated, stratified overall survival, and showed partial concordance with INR status in an INR-annotated subset (AUC 0.668).

conclusionsIntegrated serum proteomics and metabolomics revealed an INR-associated multi-omics signature and linked metabolic and immune–coagulation networks in HCC. These findings provide mechanistic insight and a candidate serum panel for future external validation.