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CENP-H 过表达可作为预测人类肝细胞癌进展和患者生存的新型预后生物标志物。

Overexpression of CENP-H as a novel prognostic biomarker for human hepatocellular carcinoma progression and patient survival.

机构信息

Department of Gastroenterology, First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

出版信息

Oncol Rep. 2013 Nov;30(5):2238-44. doi: 10.3892/or.2013.2675. Epub 2013 Aug 20.

Abstract

Centromere protein H (CENP-H) has been shown to be significantly upregulated in many types of cancers and is associated with disrupted cell cycle regulation, cell proliferation and genetic instability. The aim of the present study was to explore the expression and localization of CENP-H in hepatocellular carcinoma (HCC) and determine whether its overexpression is a prognostic biomarker for HCC. Reverse transcription-polymerase chain reaction (pcr), real-time qPCR and western blotting were used to compare CENP-H expression at the mRNA and protein levels in HCC samples and corresponding adjacent non-cancerous samples. CENP-H protein levels were determined in 60 paired paraffin-embedded HCC tissues using immunohistochemistry (IHC), and the correlation with clinicopathological features and patient prognosis was analyzed. In addition, an immunofluorescence assay was performed to test the expression and localization of CENP-H protein in HCC cells. Results showed that levels of CENP-H mRNA and protein were higher in HCC samples than in the corresponding adjacent non-cancerous samples. In 60 paired paraffin-embedded tissues, CENP-H was upregulated in the HCC samples (38/60, 63.3%) relative to the adjacent non-cancerous samples (21/60, 35%, P=0.003), and a higher level of upregulation was associated with tumor size (P=0.032); higher histological grade (P=0.001); more advanced TNM stage (P=0.002) and Chinese clinical stage (P=0.008); and poorer prognosis. In addition, consistent with the results of IHC, the immunofluorescence assay showed that CENP-H was localized in the nucleus of Hep3B cells. CENP-H was overexpressed in HCC, and its level of upregulation was an independent prognostic indicator, suggesting that CENP-H may be an effective therapeutic strategy for the treatment of HCC.

摘要

着丝粒蛋白 H(CENP-H)在许多类型的癌症中显著上调,与细胞周期调控、细胞增殖和遗传不稳定性紊乱有关。本研究旨在探讨 CENP-H 在肝细胞癌(HCC)中的表达和定位,并确定其过表达是否是 HCC 的预后生物标志物。采用逆转录-聚合酶链反应(PCR)、实时 qPCR 和 Western blot 比较 HCC 样本和相应的相邻非癌样本中 CENP-H 的 mRNA 和蛋白表达水平。采用免疫组织化学(IHC)检测 60 对石蜡包埋 HCC 组织中 CENP-H 蛋白水平,并分析与临床病理特征和患者预后的相关性。此外,还进行了免疫荧光试验以检测 HCC 细胞中 CENP-H 蛋白的表达和定位。结果表明,HCC 样本中 CENP-H mRNA 和蛋白水平高于相应的相邻非癌样本。在 60 对石蜡包埋组织中,与相邻非癌组织(21/60,35%)相比,CENP-H 在 HCC 样本中上调(38/60,63.3%),上调水平与肿瘤大小(P=0.032);组织学分级较高(P=0.001);更晚期的 TNM 分期(P=0.002)和中国临床分期(P=0.008);以及预后较差有关。此外,与 IHC 结果一致,免疫荧光试验显示 CENP-H 定位于 Hep3B 细胞的核内。CENP-H 在 HCC 中过表达,其上调水平是独立的预后指标,表明 CENP-H 可能是治疗 HCC 的有效治疗策略。

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