Combined evaluation of centromere protein H and Ki-67 as prognostic biomarker for patients with gastric carcinoma
Combined evaluation of centromere protein H and Ki-67 as prognostic biomarker for patients with gastric carcinoma
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着丝粒蛋白H和Ki-67联合评价胃癌患者的预后生物标志物
DOI：
10.1016/j.ejso.2012.08.023
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发表时间：
2013-02-01
期刊：
影响因子：
3.8
通讯作者：
Zhan, W. H.
中科院分区：
文献类型：
--
作者：
He, W. L.;Li, Y. H.;Zhan, W. H.
目的：着丝粒蛋白H（CENP-H）是人类活动着丝粒的重要组成部分之一，与肿瘤的发生密切相关。方法：应用组织芯片和免疫组化技术检测166例胃癌组织中CENP-H和Ki-67的表达。探讨其临床病理特征与预后的关系。通过实时定量PCR和Western Blot对胃癌组织和细胞系进行定量CENP-H检测。通过CENP-H敲低（SiRNA）或过表达来评估其对Survivin表达和细胞功能的影响。CENP-H在166例胃癌中有85例呈高表达，与胃癌的大小、浸润深度、淋巴结转移、远处转移及UICC分期有关与临床预后相关（系数= 0.550，P < 0.001）。多因素分析显示CENP-H和Ki 67的联合表达是患者生存的更有价值的独立预后预测因子（风险比，2.18; P = 0.0109）。此外，在GC组织和细胞系中CENP-H的总mRNA和蛋白表达显著增加。结论：CENP-H在胃癌中的高表达提示预后不良，Survivin可能介导其促癌作用。CENP-H和Ki-67的联合评估有助于预测临床预后。(C)2012爱思唯尔有限公司保留所有权利。
Aim: Centromere protein H (CENP-H) is one of the essential components of the human active kinetochore which close links with carcinogenesis. Its expression and clinical value of prognostic prediction for gastric cancer (GC) is unclear.Methods: CENP-H and Ki-67 expressions in specimens from 166 patients with GC were determined by tissue microarrays and immunostaining. Their correlations between patients' clinicopathologic features and prognosis were explored. For mechanisms, quantitative CENP-H examination on gastric cancer tissue and cell lines was performed via real-time quantitative PCR and Western Blot. Its effect on Survivin expression and cell function was evaluated via CENP-H knocking down (SiRNA) or overexpression.Results: Highly expression of CENP-H was found in 85 of 166 GC, showing a significant correlation with tumour size, depth of infiltration, lymph node metastasis, distant metastasis and UICC staging of gastric carcinoma (P < 0.05), as well as clinical prognosis (coefficient = 0.550, P < 0.001). Multivariate analysis revealed that combined CENP-H and Ki67 expression was a more valuable independent prognostic predictor for patients' survival (hazard ratio, 2.18; P = 0.0109). Furthermore, total mRNA and protein expression of CENP-H in GC tissue and cell lines were noticeably increased. Survivin expression and cell function including growth, proliferation and clonogenic ability could be inhibited by CENP-H siRNA or enhanced by overexpressing CENP-H.Conclusion: High expression of CENP-H in GC indicates poor prognosis and Survivin may mediate its procancer role. Combined evaluation of CENP-H and Ki-67 aids in predicting the clinical prognosis. (C) 2012 Elsevier Ltd. All rights reserved.