ORC1 expression features and its prognostic significance in HBV-associated hepatocellular carcinoma

Objective Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Conventional biomarkers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) have diagnostic limitations, particularly for early-stage disease. This study investigated the expression profile of ORC1 in HBV-related liver disease and its association with HBV infection, disease progression, and prognosis. Methods 178 participants were recruited: 124 HBV-positive cases (49 HBV-HCC, 33 HBV-cirrhosis, 42 chronic hepatitis B) and 54 HBV-negative controls (35 non-HBV-HCC, 19 hepatic hemangioma). Tissue ORC1 was detected by immunohistochemistry, and serum ORC1 was measured by ELISA in a subset of 17 HBV-HCC patients with available serum. Logistic regression identified factors associated with high ORC1 expression. ROC curves were used to evaluate the discrimination of tissue ORC1, AFP, and DCP for HBV-HCC, and the correlation between ORC1 and tumor diameter was analyzed. TCGA-LIHC data were used for external validation. Results Tissue ORC1 was significantly upregulated in HBV-positive patients, and HBV infection was independently associated with high ORC1 expression (P<0. 001). ORC1 expression increased progressively from chronic hepatitis B to cirrhosis to HCC. In a subset of 17 HBV-HCC patients with available serum, tissue and serum ORC1 were moderately correlated (Spearman rs=0. 554, 95% CI 0. 085–0. 822, P = 0. 021). Tissue ORC1 showed moderate discrimination between HBV-HCC and HBV-LC (AUC = 0. 64) and between HBV-HCC and CHB (AUC = 0. 66). ORC1 expression was not significantly associated with tumor diameter ( P >0. 05). High ORC1 expression was associated with poorer overall survival in TCGA-LIHC (HR = 1. 7, P = 0. 0026). Conclusion ORC1 upregulation is independently associated with HBV infection and increases with disease progression in HBV-related liver disease. Although tissue ORC1 showed only moderate discrimination for HBV-HCC, high ORC1 expression was associated with poorer overall survival in TCGA-LIHC. These findings suggest that ORC1 is primarily a proliferation- and progression-related marker in HBV-related liver disease.