Objective: This study aimed to evaluate the individual and combined diagnostic values of serum alpha-fetoprotein (AFP), des-gamma-carboxyprothrombin (DCP), glypican-3 (GPC3) and golgi protein 73 (GP73) in diagnosing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods: Participants from Beijing YouAn Hospital were enrolled and divided into seven groups. Serum was collected and the levels of AFP, GPC3, GP73 and DCP were simultaneously measured with a protein array. Pearson’s χ² test was applied to compare the clinicopathological characteristics. Receiver operating characteristic (ROC) curves were used to analyse the diagnostic performance of the four markers. Results: As a single biomarker for differentiating HCC from all controls, AFP had a larger area under the curve (AUC) (0.798, 95% CI (0.754– 0.838) than the other biomarkers, with a sensitivity of 77.3% and a specificity of 71.1%. Among the other combinations, AFP plus GPC3 and DCP (0.871, 95% CI (0.833– 0.903)) was the best at differentiating HCC from all controls. In discriminating very early stage and early stage HCC from all controls, the AUC of GPC3 (0.744, 95% CI (0.690– 0.793); sensitivity 62.8%; specificity 83.3%) was better than that of AFP (0.723, 95% CI (0.668– 0.774); sensitivity 67.3%; specificity 71.7%). Among all biomarker combinations, the combination of AFP, GPC3 and GP73 had the largest AUC (0.843, 95% CI (0.796– 0.883); sensitivity 84.1%; specificity 71.7%). AFP (AUC 0.726, 95% CI (0.662– 0.784)) showed the best performance in the very early diagnosis of HBV-related HCC. Conclusion: As a single biomarker, AFP has an advantage in the very early and early diagnosis of HBV-related HCC. The combination of AFP, GPC3 and GP73 is the most suitable marker for the early diagnosis of HBV-related HCC. However, AFP remains the best biomarker for the very early diagnosis of HBV-related HCC, and the adding of one or more markers does not significantly improve the diagnostic accuracy.

G-protein coupled receptor-associated sorting protein 1 (GASP1) is a secreted protein that has been reported to be associated with various malignant tumors. However, its role in primary liver cancer (PLC) remains largely unexplored. The aim of this study was to evaluate the expression and clinical significance of GASP1 in PLC, as well as to investigate its potential as a clinical biomarker. To achieve this, we conducted RT-qPCR experiments to assess the transcriptional levels of GASP1 in tumor tissues from cancer patients compared to adjacent non-tumor liver tissues. Statistical analyses were performed to examine the associations between GASPl levels and various clinicopathological factors. Our results demonstrated that the mRNA expression level of GASP1 was significantly higher in PLC tumor center tissues compared to matched adjacent non-tumor liver tissues (P=0.034). Additionally, Fisher's exact test revealed a significant association between GASP1 expression and lymphocyte infiltration (P=0.018), suggesting that GASP1 may play an important role in the tumor microenvironment (TME) of PLC. Notably, we observed that among PLC patients exhibiting lymphocyte infiltration, a majority were hepatitis B patients or carriers of the hepatitis B virus (HBV). This observation indicates a potential relationship between GASP1 expression and HBV infection in the pathogenesis of PLC. We also identified elevated GASP1 expression in the majority of AFP-positive patients and HBsAg-positive patients, suggesting a potential correlation between GASP1 expression and both AFP levels and HBV status in PLC. Furthermore, our findings indicated that GASP1 expression exhibits a negative correlation with HBsAb (r=-0.609, P=0.035), TBIL (r=-0.636, P=0.026), DBIL (r=-0.622, P=0.031), and IBIL (r=-0.727, P=0.007), while demonstrating a positive correlation with lymphocyte infiltration (τ=0.816, P=0.007). In summary, our findings emphasize that GASP1 may serve as a novel biomarker for PLC and its expression levels are associated with clinicopathological features. This insight offers a new perspective for the diagnosis and treatment of PLC.

Introduction: Chronic hepatitis B virus (HBV) infection is the leading cause of primary liver cancer (PLC), notably hepatocellular carcinoma. G-protein coupled receptor-associated sorting protein 1 (GPRASP1), a G protein-coupled receptor-associated protein, has been implicated in multiple malignancies. However, its role in PLC, particularly in hepatitis B surface antigen (HBsAg)-positive patients, remains unclear. Objective: To explore the GPRASP1 expression pattern and its clinical significance in PLC, with a focus on HBsAg-positive cases, and to evaluate its potential as a candidate biomarker. Methods: Tumor center tissues and paired adjacent non-tumor liver tissues were collected from 12 pathologically confirmed PLC patients, including seven with active HBV infection or chronic carrier status. GPRASP1 mRNA expression levels were quantified using reverse-transcription quantitative polymerase chain reaction. Associations between GPRASP1 expression and clinicopathological variables were statistically analyzed. Results: GPRASP1 mRNA expression was significantly up-regulated in central tumor tissues and paired adjacent non-tumor liver tissues (p = 0.034). Elevated GPRASP1 expression was detected in 80% of HBsAg-positive PLC patients. GPRASP1 levels were significantly inversely correlated with hepatitis B surface antibody titers. Higher GPRASP1 expression was positively correlated with lymphocyte infiltration (τ = 0.816, p = 0.007). Moreover, GPRASP1 expression was negatively correlated with serum total bilirubin (r = −0.636, p = 0.026), direct bilirubin (r = −0.622, p = 0.031), and indirect bilirubin (r = −0.727, p = 0.007). Conclusion: GPRASP1 is overexpressed in PLC tissues, particularly in HBsAg-positive patients, and its expression is associated with host immune response and hepatic functional markers. GPRASP1 may serve as a potential diagnostic biomarker for PLC and may provide novel insights into its diagnosis.