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DBC1的过表达与预后不良相关,是肝细胞癌的一个潜在治疗靶点。

Overexpression of DBC1, correlated with poor prognosis, is a potential therapeutic target for hepatocellular carcinoma.

作者信息

Li Changcan, Liao Jianhua, Wu Shaohan, Fan Junwei, Peng Zhihai, Wang Zhaowen

机构信息

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Department of General Surgery, Zhejiang Hospital, Hangzhou 310013, China.

出版信息

Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):511-517. doi: 10.1016/j.bbrc.2017.10.134. Epub 2017 Oct 26.

DOI:10.1016/j.bbrc.2017.10.134
PMID:29106957
Abstract

Deleted in Breast Cancer 1 (DBC1) is a regulatory protein involved in cell metabolism and cancer progression. Nevertheless, the expression and prognostic values of DBC1 in hepatocellular carcinoma (HCC) are still not well understood. The following study investigated the clinical significance and biological function of DBC1 in HCC. Briefly, overexpression of DBC1 at transcriptional and translational levels in human HCC tissues compared to adjacent normal tissues was observed using quantitative real-time polymerase chain reaction (qRT-PCR), western blot (WB) and immunohistochemistry (IHC) approach. Furthermore, upregulated DBC1 was significantly correlated with tumor size (p = 0.005), N stage (p = 0.016), M stage (p = 0.011), tumor differentiation (p < 0.001), and American Joint Committee on Cancer (AJCC) stage (p = 0.001). Moreover, Kaplan-Meier survival analysis revealed that DBC1 was an independent prognosis predictor for disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). In addition, by using Cell Counting Kit-8 (CCK8) assays and colony formation assays, we found that the knockdown of DBC1 significantly suppressed the proliferation of HCC cells in vitro. To conclude, these findings demonstrated that DBC1 was essential in tumorigenesis and proliferation. Moreover, it was identified as a potential therapeutic target for HCC.

摘要

乳腺癌缺失基因1(DBC1)是一种参与细胞代谢和癌症进展的调节蛋白。然而,DBC1在肝细胞癌(HCC)中的表达及预后价值仍未完全明确。以下研究探讨了DBC1在HCC中的临床意义和生物学功能。简而言之,采用定量实时聚合酶链反应(qRT-PCR)、蛋白质免疫印迹法(WB)和免疫组织化学(IHC)方法,观察到与癌旁正常组织相比,人HCC组织中DBC1在转录和翻译水平均有过表达。此外,DBC1表达上调与肿瘤大小(p = 0.005)、N分期(p = 0.016)、M分期(p = 0.011)、肿瘤分化程度(p < 0.001)以及美国癌症联合委员会(AJCC)分期(p = 0.001)显著相关。而且,Kaplan-Meier生存分析显示,DBC1是无病生存期(DFS)(p < 0.001)和总生存期(OS)(p < 0.001)的独立预后预测指标。另外,通过细胞计数试剂盒-8(CCK8)检测和集落形成实验,我们发现敲低DBC1可显著抑制体外HCC细胞的增殖。总之,这些研究结果表明DBC1在肿瘤发生和增殖过程中至关重要。此外,它被确定为HCC的一个潜在治疗靶点。

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