Expression of key factors in the TGF-β1/Smad2 pathway and their associations with clinicopathological characteristics and prognosis in HBV-associated hepatocellular carcinoma

Abstract Background This study investigated the expression of TGF-β1 and Smad2 in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and evaluated their associations with clinicopathological characteristics and prognosis. Methods In this prospective single-center cohort, 120 patients with HBV-associated HCC were enrolled between April 2022 and April 2024. TGF-β1 and Smad2 expression was assessed by immunohistochemistry in paired tumor and adjacent non-tumor tissues. Associations with clinicopathological characteristics and prognosis were examined using correlation analysis, logistic regression, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) analysis. Follow-up lasted 12–36 months. Results TGF-β1 and Smad2 expression was significantly higher in tumor tissue than in paired adjacent non-tumor tissue (both P < 0.001). Higher expression was associated with poorer differentiation and more advanced stage ( P < 0.05). Patients with positive TGF-β1 or Smad2 expression had lower survival rates than those with negative expression. The AUCs for predicting death were 0.769 for TGF-β1, 0.756 for Smad2, and 0.892 for the combined model. Conclusions Elevated tumor expression of TGF-β1 and Smad2 is associated with aggressive clinicopathological features and poorer prognosis in HBV-associated HCC. Combined assessment of the two markers may improve prognostic discrimination compared with either marker alone; multicenter validation is warranted.