Prognostic Significance of Poly (ADP-Ribose) Polymerase 1 Binding Protein Expression and CD8+ Tumor-Infiltrating Lymphocytes in Hepatocellular Carcinoma

Abstract

The role of poly (adenosine diphosphate [ADP]-ribose) polymerase 1 binding protein (PARPBP) in hepatocellular carcinoma (HCC) prognosis remains unclear. This study investigated PARPBP expression in HCC clinical samples and evaluated its clinicopathological significance in relation to CD8-positive tumor-infiltrating lymphocytes (CD8⁺ TILs). PARPBP expression and CD8⁺ TIL density were assessed in surgical specimens from 96 patients with HCC. We performed immunohistochemical analysis to determine PARPBP protein levels, which were correlated with clinicopathological features and patient outcomes. Additionally, we performed experiments using a doxycycline-inducible short hairpin RNA system targeting PARPBP in Huh7 cells. Results indicated that moderately and poorly differentiated HCC had significantly higher PARPBP expression than well-differentiated tumors. Patients with high PARPBP expression exhibited shorter recurrence-free survival and overall survival than those with low expression (both P < .001). Multivariate analysis showed that high PARPBP expression (hazard ratio [HR], 2.806; P = .002), high CD8⁺ TIL density (HR, 0.148; P < .001), and α-fetoprotein ≥ 10 ng/mL (HR, 1.904; P = .047) were independent predictors of prognosis. Combined analysis revealed that patients with high PARPBP expression and low CD8⁺ TIL density had the worst recurrence-free survival and overall survival outcomes (both P < .001). In vitro experiments showed that the mRNA expression of PARPBP was higher in liver cancer cell lines than in normal liver cells and that PARPBP knockdown suppressed huh7 cell proliferation. In conclusion, elevated PARPBP expression was associated with poor differentiation and survival in patients with HCC. Furthermore, the combination of high PARPBP expression and low CD8⁺ TIL density improved prognostic accuracy.