Abstract
Transcatheter arterial chemoembolization (TACE) induces ischemia-hypoxia and local chemotherapy-induced cytotoxicity which destroys cancerous cells. However, some patients do not respond to TACE. The causes for such a lack of response remain unclear. Recent studies have revealed that self-regulation of apoptosis-stimulating p53 protein 2 (ASPP2) may play an important role in promoting cell survival under hypoxic conditions as well as chemotherapy resistance via autophagy in various types of cancer. We measured the expression of ASPP2, autophagy-related proteins and apoptotic proteins by western blot assays. Multivariate logistic regression analysis was used to identify the independent risk factor. The present study found that ASPP2 expression was negatively correlated with that of BECN-1 (Beclin-1) in hepatocellular carcinoma (HCC) tissues. The expression of ASPP-1 was lower while that of Beclin-1 was higher in patients who underwent recurrence of HCC following TACE, than in those who do not undergo such a relapse. ASPP2 expression was also lower in cancerous tissues subjected to TACE, compared with that of directly resected cancerous tissue. The expression of LC3-II was also higher in patients with post-operative recurrence of HCC than in those without relapse. In vitro experiments showed that administration of an autophagy inhibitor, together with hypoxia activation and 5-FU treatment, promoted apoptosis in HepG2 liver cancer cells and primary HCC cells. Multivariate logistic regression analysis revealed that ASPP2 expression in cancer tissue following TACE is an independent risk factor for HCC recurrence as well as overall survival. Higher levels of ASPP2 expression were notably associated with higher objective responses evaluated via mRECIST. Thus, patients with resectable HCC showing high levels of ASPP2 expression may benefit from neoadjuvant TACE prior to resection. Our study provided a novel biomarker for HCC prognosis following TACE, based on cell survival mechanisms related to autophagy.