ANXA2 as a Candidate Molecular Hub Linking Fibrinolysis, Coagulation, and Immune Remodeling in Hepatocellular Carcinoma: An Integrative Multi-Omics Analysis

Annexin A2 (ANXA2) is involved in cell-surface fibrinolysis and has been associated with hepatocellular carcinoma (HCC). We examined ANXA2 expression in HCC and its associations with survival and immune–hemostatic gene expression. ANXA2 transcript expression was assessed in The Cancer Genome Atlas liver cancer cohort (TCGA-LIHC) and an independent HCC dataset (GSE25097). Public protein datasets were used to examine ANXA2 abundance. We analyzed clinicopathological associations, overall survival, tumor–normal tissue discrimination, and correlations with selected immune, coagulation, fibrinolytic, and inflammatory genes. ANXA2 expression was higher in HCC than in non-tumor liver tissue in the transcriptomic analyses and was elevated in the protein analyses. Higher ANXA2 expression was associated with poorer overall survival after adjustment for age, sex, and pathological stage (hazard ratio, 1.26; 95% confidence interval, 1.07–1.49; p = 0.006). Within TCGA-LIHC, ANXA2 expression discriminated tumor from normal tissue (area under the curve, 0.895; 95% confidence interval, 0.852–0.933); this performance was not independently validated. ANXA2 expression also correlated with selected fibrinolytic, inflammatory, and immune-related genes. GSE25097 supported the differential-expression finding. ANXA2 is overexpressed in HCC and is associated with poorer survival and an immune–hemostatic transcriptional pattern. The correlations do not establish that ANXA2 regulates these processes.