Decreased TPD52 expression is associated with poor prognosis in primary hepatocellular carcinoma.
Decreased TPD52 expression is associated with poor prognosis in primary hepatocellular carcinoma.
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TPD52 表达降低与原发性肝细胞癌预后不良相关。
DOI：
10.18632/oncotarget.6319
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发表时间：
2016-02-02
期刊：
影响因子：
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通讯作者：
Xia JC
中科院分区：
文献类型：
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作者：
Wang Y;Chen CL;Pan QZ;Wu YY;Zhao JJ;Jiang SS;Chao J;Zhang XF;Zhang HX;Zhou ZQ;Tang Y;Huang XQ;Zhang JH;Xia JC
肿瘤蛋白D52(TPD52)被认为与多种恶性肿瘤的发生有关。但其在肝细胞癌中的作用尚不清楚。本研究旨在应用实时定量聚合酶链式反应、免疫印迹和免疫组织化学方法检测TPD52在肝细胞癌标本和细胞系中的表达。并分析了TPD52在肝细胞癌中的预后价值。同时，通过Western blotting、免疫组织化学、过表达和基因敲除研究，进一步探讨了TPD52在肝癌发生中的作用机制。我们发现TPD52在肝癌组织和肝癌细胞系中的表达显著降低。TPD52表达与肿瘤转移(TNM)分期显著相关。Kaplan-Meier生存曲线显示，TPD52的高表达与肝癌患者总生存期(OS)和无瘤生存期(DFS)的改善有关。多因素分析显示，TPD52表达是影响患者OS和DFS的独立预后指标。肝癌组织中TPD52的表达与p21、p53的表达呈正相关，与mdm2、bcl2、P-GSK-3的β表达呈负相关。综上所述，我们的研究结果提示TPD52是一种潜在的肝细胞癌肿瘤抑制因子。它可能成为一种新的肝细胞癌预后生物标志物和分子治疗靶点。
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.