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MTDH在肝癌进展中的关键作用:一项免疫组织化学、癌症基因组图谱(TCGA)、荟萃分析及调查研究

The essential role of MTDH in the progression of HCC: a study with immunohistochemistry, TCGA, meta-analysis and investigation.

作者信息

He Rongquan, Gao Li, Ma Jie, Peng Zhigang, Zhou Shengsheng, Yang Lihua, Feng Zhenbo, Dang Yiwu, Chen Gang

机构信息

Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, P. R. China.

Department of Pathology, First Affiliated Hospital of Guangxi Medical University6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, P. R. China.

出版信息

Am J Transl Res. 2017 Apr 15;9(4):1561-1579. eCollection 2017.

Abstract

Recent studies found that metadherin (MTDH) played an essential role in hepatocellular carcinoma (HCC). Nevertheless, the exact function of MTDH in the pathogenesis of HCC was unclarified. In the present study, we aimed to investigate the clinical significance of MTDH in HCC and its effect on HCC cells. Immunohistochemistry (IHC) was performed to detect MTDH expression in HCC tissues. Data from The Cancer Genome Atlas (TCGA) and ONCOMINE was obtained to examine MTDH expression in HCC and its clinical significance. Meta-analysis was conducted to assess the correlation between MTDH expression and both the prognosis (Overall Survival (OS) or Disease-free Survival (DFS)) and clinicopathological features of HCC via STATA 12.0. experiments were performed to investigate the role of MTDH in cell growth, caspase-3/7 activity and apoptosis in HCC cells. The MTDH staining was remarkably stronger in HCC tissues than in non-cancer tissues from IHC, TCGA and ONCOMINE data. Moreover, MTDH-positive expression was significantly correlated with pathological grade, distant metastasis and hepatitis B virus (HBV) infection by IHC. For meta-analysis, MTDH expression was indicative of poor OS without heterogeneity in HCC patients. Additionally, MTDH expression was correlated with high-grade histological differentiation, non-vascular invasion and metastasis in HCC. experiments revealed that MTDH could the inhibit cell growth and activate caspase-3/7 activity and apoptosis in the four HCC cell lines. In conclusion, MTDH expression may serve as a novel targeting strategy for HCC due to its clinical significance and oncogenic function in HCC cells.

摘要

最近的研究发现,黏附素(MTDH)在肝细胞癌(HCC)中起着至关重要的作用。然而,MTDH在HCC发病机制中的确切功能尚不清楚。在本研究中,我们旨在探讨MTDH在HCC中的临床意义及其对HCC细胞的影响。采用免疫组织化学(IHC)检测HCC组织中MTDH的表达。获取来自癌症基因组图谱(TCGA)和ONCOMINE的数据,以检查HCC中MTDH的表达及其临床意义。通过STATA 12.0进行荟萃分析,以评估MTDH表达与HCC的预后(总生存期(OS)或无病生存期(DFS))以及临床病理特征之间的相关性。进行实验以研究MTDH在HCC细胞的细胞生长、半胱天冬酶-3/7活性和凋亡中的作用。根据IHC、TCGA和ONCOMINE数据,HCC组织中的MTDH染色明显强于非癌组织。此外,通过IHC检测,MTDH阳性表达与病理分级、远处转移和乙型肝炎病毒(HBV)感染显著相关。对于荟萃分析,MTDH表达表明HCC患者的OS较差,且无异质性。此外,MTDH表达与HCC的高分化组织学、无血管侵犯和转移相关。实验表明,MTDH可抑制四种HCC细胞系的细胞生长,并激活半胱天冬酶-3/7活性和凋亡。总之,由于MTDH在HCC细胞中的临床意义和致癌功能,其表达可能成为HCC的一种新型靶向策略。

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