Mao Jiaren, Tan Zhongjun, Pan Xiaoqi, Meng Feijian
Department of Radiology, The People's Hospital of Danyang, Danyang, Jiangsu 212300, P.R. China.
Exp Ther Med. 2021 Apr;21(4):397. doi: 10.3892/etm.2021.9828. Epub 2021 Feb 24.
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 () 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. 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.
经动脉化疗栓塞术（TACE）可诱导缺血缺氧以及局部化疗诱导的细胞毒性，从而破坏癌细胞。然而，一些患者对TACE无反应。这种缺乏反应的原因尚不清楚。最近的研究表明，凋亡刺激蛋白p53 2（ASPP2）的自我调节可能在促进缺氧条件下的细胞存活以及通过自噬在各种类型癌症中产生化疗耐药性方面发挥重要作用。我们通过蛋白质免疫印迹分析测量了ASPP2、自噬相关蛋白和凋亡蛋白的表达。采用多因素逻辑回归分析来确定独立危险因素。本研究发现，在肝细胞癌（HCC）组织中，ASPP2表达与BECN-1（Beclin-1）表达呈负相关。TACE后发生HCC复发的患者中，ASPP-1表达较低，而Beclin-1表达较高，高于未发生此类复发的患者。与直接切除的癌组织相比，接受TACE的癌组织中ASPP2表达也较低。HCC术后复发患者的LC3-II表达也高于未复发患者。实验表明，给予自噬抑制剂，同时激活缺氧和5-氟尿嘧啶治疗，可促进HepG2肝癌细胞和原发性HCC细胞的凋亡。多因素逻辑回归分析显示，TACE后癌组织中ASPP2表达是HCC复发以及总生存期的独立危险因素。ASPP2表达水平较高与通过改良实体瘤疗效评价标准（mRECIST）评估的较高客观反应显著相关。因此，ASPP2表达水平高的可切除HCC患者在切除前可能从新辅助TACE中获益。我们的研究基于与自噬相关的细胞存活机制，为TACE后HCC的预后提供了一种新的生物标志物。
