Wang Ying, Chen Chang-Long, Pan Qiu-Zhong, Wu Ying-Yuan, Zhao Jing-Jing, Jiang Shan-Shan, Chao Jie, Zhang Xiao-Fei, Zhang Hong-Xia, Zhou Zi-Qi, Tang Yan, Huang Xu-Qiong, Zhang Jian-Hua, Xia Jian-Chuan
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Department of Epidemiology and Health Statistics, Guangdong Key Laboratory of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou, China.
Oncotarget. 2016 Feb 2;7(5):6323-34. doi: 10.18632/oncotarget.6319.
Tumor protein D52 (TPD52) has been indicated to be involved in tumorigenesis of various malignancies. But its role in hepatocellular carcinoma (HCC) is unknown. This study aimed to explore the expression of TPD52 in HCC samples and cell lines using real-time quantitative PCR, western blotting, and immunohistochemistry. The prognostic value of TPD52 in HCC was also analysed. Meanwhile, the mechanism of TPD52 in hepatocarcinogenesis was further investigated by western blotting, immunohistochemistry, over-express and knockdown studies. We found that TPD52 expression was significantly decreased in the HCC tissues and HCC cell lines. TPD52 expression was significantly correlated with tumor-nodes-metastasis (TNM) stage. Kaplan-Meier survival curves showed that high TPD52 expression was associated with improved overall survival (OS) and disease-free survival (DFS) in HCC patients. Multivariate analysis indicated that TPD52 expression was an independent prognostic marker for the OS and DFS of patients. In addition, TPD52 expression was positively correlated with p21 and p53 expression, and was negatively correlated with MDM2, BCL2 and P-GSK-3β expression in HCC. In conclusions, our findings suggested that TPD52 is a potential tumor suppressor in HCC. It may be a novel prognostic biomarker and molecular therapy target for HCC.
肿瘤蛋白D52(TPD52)已被证实与多种恶性肿瘤的发生有关。但其在肝细胞癌(HCC)中的作用尚不清楚。本研究旨在通过实时定量PCR、蛋白质免疫印迹法和免疫组织化学法,探讨TPD52在HCC组织样本和细胞系中的表达情况。同时分析TPD52在HCC中的预后价值。此外,通过蛋白质免疫印迹法、免疫组织化学法、过表达和敲低研究,进一步探究TPD52在肝癌发生中的机制。我们发现,TPD52在HCC组织和HCC细胞系中的表达显著降低。TPD52表达与肿瘤-淋巴结-转移(TNM)分期显著相关。Kaplan-Meier生存曲线显示,TPD52高表达与HCC患者总生存期(OS)和无病生存期(DFS)的改善相关。多因素分析表明,TPD52表达是患者OS和DFS的独立预后标志物。此外,在HCC中,TPD52表达与p21和p53表达呈正相关,与MDM2、BCL2和P-GSK-3β表达呈负相关。总之,我们的研究结果表明,TPD52是HCC中一种潜在的肿瘤抑制因子。它可能是HCC一种新的预后生物标志物和分子治疗靶点。