Oncogenic secretory clusterin in hepatocellular carcinoma: Expression at early staging and emerging molecular target.

// Wenjie Zheng 1, * , Min Yao 2, * , Qi Qian 3, * , Wenli Sai 1 , Liwei Qiu 1 , Junling Yang 1 , Wei Wu 1 , Zhizhen Dong 1, 4 and Dengfu Yao 1 1 Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China 2 Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China 3 Department of Oncology, Yancheng 1 st People’s Hospital, Yancheng 224005, Jiangsu Province, China 4 Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China * These authors have contributed equally to this work Correspondence to: Dengfu Yao, email: yaodf@ahnmc.com Zhizhen Dong, email: dongzz@ahnmc.com Keywords: hepatocellular carcinoma, secretory clusterin, prognosis, tumor stage, tumor growth Received: September 20, 2016      Accepted: November 18, 2016      Published: November 29, 2016 ABSTRACT Secretory clusterin (sCLU) is associated with hepatocellular carcinoma (HCC) progression by contributing to angiogenesis, chemoresistance, cell survival, and metastasis. However, the sCLU expression at early stage of HCC progression remains to be clarified. In this study, the alteration of sCLU oncogenicity was firstly evaluated in HCC- and their para-cancerous- tissues. The incidence of sCLU expression in HCC was significantly higher than that in their non-tumorous tissues at message RNA (mRNA) or protein level, gradually increasing with tumor-node-metastasis (TNM) staging. Abnormal sCLU expression was associated with the poor differentiation, TNM stage, and considered as an independent prognostic factor for HCC patients. Furthermore, silencing sCLU gene transcription inhibited the colony formation and proliferation of HCC cells, with decreasing phosphorylation level of AKT and GSK-3β in HCCLM3 cells in vitro and significantly suppressed the HCC xenograft growth in vivo, suggesting that sCLU with oncogenicity should be not only an early indicator but also novel potential molecular-targeted therapy for HCC.