Expression of Platelet-Activating Factor Receptor: A Novel Prognosticator in Patients with Hepatocellular Carcinoma following Hepatectomy

Abstract

Backgrounds and Aims: Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a phospholipid mediator and acts by binding to a specific G-protein-coupled receptor. Though various functions of PAF have been associated with tumor activities, the mechanism of PAF-PAF receptor signaling in the development of hepatocellular carcinoma (HCC) remains to be elucidated. Methods: In this study, PAF receptor (PAFR) expression was examined in hepatoma cell lines (Huh7, PLC/PRF/5 and HepG2) and clinical samples of HCC (n = 60) using immunohistochemical staining. The relationships between the expression of PAFR and clinicopathological parameters were also investigated. Results: An immunohistochemical study showed that 24 HCC cases (40%) showed a lower PAFR expression than non-cancerous hepatocytes. The patients were divided into two groups according to the degree of PAFR expression: the high (n = 36) and low PAFR groups (n = 24). Lower expression of PAFR was correlated with poor differentiation, portal vein invasion, high levels of serum α-fetoprotein and poor prognosis after surgery. In the low PAFR group, multiple recurrences and distant metastases were more often observed than in the high PAFR group. Multivariate analysis revealed that lower PAFR expression in addition to portal vein invasion is significantly related to survival after hepatectomy. Conclusions: A lower expression of PAFR correlated with poor differentiation and a poor prognosis, and may therefore be used as a prognostic marker in HCC after hepatectomy.