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.

Platelet-activating factor (PAF) receptor expression is associated with histopathological stage and grade and patients’ survival in gastric adenocarcinoma

“…Weak PAFR expression was also noted in epithelial cells in 6 cases of gastritis [Giaginis et al, unpublished data]. In accordance with our findings, an immunohistochemical study conducted on 60 hepatocellular carcinoma patients revealed significant association between low PAFR expression and poor tumor [41]. Moreover, this study indicated that multiple recurrences and distant metastases were more often observed in patients presenting low compared to those with high PAFR expression [41].…”

“…In accordance with our findings, an immunohistochemical study conducted on 60 hepatocellular carcinoma patients revealed significant association between low PAFR expression and poor tumor [41]. Moreover, this study indicated that multiple recurrences and distant metastases were more often observed in patients presenting low compared to those with high PAFR expression [41]. Another immunohistochemical study revealed that PAFR expression was significantly increased in ovarian cancer patients compared to benign ovarian tissue specimens, being varied across different histological subtypes of the ovarian cancer [40].…”

“…PAF/PAFR pathway has been implicated in several pathophysiological situations, including tumor progression, angiogenesis and metastasis. However, most of the existing data so far has been derived from in vitro studies and animal models, whereas only a few clinical studies had focussed on the assessment of PAFR expression levels in human malignancies [29,[35][36][37][38][39][40][41][42][43]. Moreover, there is neither experimental nor clinical evidence so far concerning the implication of PAF/PAFR pathway in the development and progression of gastric neoplasia.…”

“…Intratumoral PAF production was shown to be ascribed to both tumor cells and those of the microenvironment, including infiltrating macrophages, supporting evidence that PAF may be responsible for potentiating tumor growth, neoangiogenesis, and cell motility [25,34]. In humans, the contribution of PAF/PAFR pathway is mainly suspected in lung, breast, ovarian, colorectal, hepatocellular and thyroid carcinoma, as also in melanoma [29,[35][36][37][38][39][40][41][42][43]. Importantly, it has been suggested that inhibiting PAF/PAFR pathway at the level of a ligand or receptor may result in an effective inhibition of experimental tumor growth and metastasis [22,23].…”

Platelet-activating factor receptor activation promotes prostate cancer cell growth, invasion and metastasis via ERK1/2 pathway

“…In addition, studies have found that crosstalk between protease-activated receptor 1 and PAFR regulates melanoma metastasis (14) and PAFR activation augments the growth and metastasis of lung cancer (15). However, some studies have found that lower expression of PAFR correlats with poor differentiation and a poor prognosis in patients with hepatocellular carcinoma after hepatectomy (16), and PAFR expression is negative associated with histopathological stage and grade and patient survival in gastric adenocarcinoma (9). In prostate cancer cells, Jan and Chao (17) found that a specific PAFR antagonist inhibits prostate cancer cell growth, but the function of PAFR in the progression of prostate cancer cells and the underlying molecular mechanisms are still not very clear.…”