Adiponectin Receptor Expression Predicts Favorable Prognosis in Cases of Hepatocellular Carcinoma

Abstract

Obesity influences risk, progression and prognosis of various cancers including hepatocellular carcinoma (HCC). Adipose-tissue-derived adipokines has been considered to be involved in tumorigenesis and adiponecin, one such adipokine, has antiproliferative effect on obesity-related malignancies, though variable signal pathway mediated by adiponectin receptors-AdipoR1 and AdipoR2. In this study, we investigated expression of adiponectin and adiponectin receptors in tumor and non-tumorous hepatic tissues of HCC patients and its clinicopathological significance. We collected 75 HCC tissues and 70 non-tumorous hepatic tissues from HCC patients who underwent surgical resection. The tissue microarrays were constructed and immunohistochemical study for adiponectin, AdipoR1 and AipoR2 was performed. Adiponectin and AdipoR1 expression rates were significantly lower in HCC than non-neoplastic hepatic tissues (82.7 % vs. 97.1 % and 24.0 % vs. 90 %, P = 0.005 and < 0.001, respectively). Immunopositivity for adiponectin was associated with small tumor size, low Edmonson-Steiner grade and absence of other organ invasion (P = 0.015, 0.021 and 0.028, respectively). AdipoR1 expression had association with absence of vascular invasion (P = 0.028) and AdipoR2 expression was correlated with lower histologic grade and low pathologic T-stage (P = 0.003 and 0.008, respectively). Cox regression analysis revealed that low expression of AdipoR1 and AdipoR2 were associated with increased risk of recurrence and death, respectively (hazard ration = 3.222 and 14.797, respectively). These findings suggest that loss of adiponectin, and adiponectin receptors expression is associated with aggressive clinicopathological features of HCC and AdipoR1 and AdipoR2 might serve as the independent prognostic factors for HCC patients.