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人神经胶质瘤中整联蛋白和金属蛋白酶 8 的过表达与肿瘤进展和预后相关。

Overexpression of a disintegrin and metalloprotease 8 in human gliomas is implicated in tumor progression and prognosis.

机构信息

Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.

出版信息

Med Oncol. 2012 Sep;29(3):2032-7. doi: 10.1007/s12032-011-0084-9. Epub 2011 Oct 9.

DOI:10.1007/s12032-011-0084-9
PMID:21983884
Abstract

A disintegrin and metalloprotease 8 (ADAM8) has been shown to be expressed in various cancer types, and its expression was associated with advanced progression of several tumors. However, little is known about ADAM8 in human gliomas. Therefore, we here evaluated the correlation of ADAM8 expression with the clinicopathological features and prognosis in the patients with gliomas. Immunohistochemistry and western blot were used to investigate the expression of ADAM8 protein, respectively, in 128 patients with gliomas. The expression levels of ADAM8 in glioma tissues were significantly higher (P = 0.002) than those in non-neoplastic brain tissues according to the immunohistochemistry analysis. In addition, a high level of ADAM8 expression was significantly more common in glioma tissues with advanced grade than those with low grade (P = 0.01), which were in line with the results of western blot analysis (P = 0.01). Moreover, the increased expression of ADAM8 was significantly correlated with low Karnofsky performance score (KPS) (P = 0.008), frequent intra-tumor necrosis (P = 0.01), and poor overall survival (P = 0.008). Furthermore, multivariate analysis identified the expression levels of ADAM8 (P = 0.01) and intra-tumor necrosis (P = 0.03) to be independent prognostic factors. These findings suggest for the first time that ADAM8 is frequently overexpressed in human gliomas and is closely associated with poor clinical outcome.

摘要

去整合素金属蛋白酶 8(ADAM8)已被证明在多种癌症类型中表达,其表达与几种肿瘤的晚期进展有关。然而,关于 ADAM8 在人类神经胶质瘤中的作用知之甚少。因此,我们在这里评估了 ADAM8 表达与胶质瘤患者临床病理特征和预后的相关性。分别使用免疫组织化学和蛋白质印迹法检测 128 例胶质瘤患者 ADAM8 蛋白的表达。根据免疫组织化学分析,ADAM8 在胶质瘤组织中的表达水平明显高于非肿瘤性脑组织(P = 0.002)。此外,高级别胶质瘤组织中 ADAM8 高表达明显比低级别胶质瘤组织更常见(P = 0.01),这与蛋白质印迹分析结果一致(P = 0.01)。此外,ADAM8 的表达增加与较低的 Karnofsky 表现评分(KPS)(P = 0.008)、肿瘤内频繁坏死(P = 0.01)和较差的总生存期(P = 0.008)显著相关。此外,多因素分析确定 ADAM8 的表达水平(P = 0.01)和肿瘤内坏死(P = 0.03)是独立的预后因素。这些发现首次表明 ADAM8 在人类神经胶质瘤中经常过表达,与不良临床结局密切相关。

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The GBM Tumor Microenvironment as a Modulator of Therapy Response: ADAM8 Causes Tumor Infiltration of Tams through HB-EGF/EGFR-Mediated CCL2 Expression and Overcomes TMZ Chemosensitization in Glioblastoma.胶质母细胞瘤肿瘤微环境作为治疗反应的调节因子:ADAM8通过HB-EGF/EGFR介导的CCL2表达导致肿瘤相关巨噬细胞的肿瘤浸润并克服胶质母细胞瘤中替莫唑胺的化学增敏作用。
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The Metalloprotease-Disintegrin ADAM8 Alters the Tumor Suppressor miR-181a-5p Expression Profile in Glioblastoma Thereby Contributing to Its Aggressiveness.金属蛋白酶-解整合素ADAM8改变胶质母细胞瘤中肿瘤抑制因子miR-181a-5p的表达谱,从而促进其侵袭性。
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本文引用的文献

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Novel alternatively spliced ADAM8 isoforms contribute to the aggressive bone metastatic phenotype of lung cancer.新型交替剪接的 ADAM8 异构体有助于肺癌侵袭性骨转移表型。
Oncogene. 2010 Jul 1;29(26):3758-69. doi: 10.1038/onc.2010.130. Epub 2010 May 10.
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ADAM8 substrate specificity: influence of pH on pre-processing and proteoglycan degradation.ADAM8底物特异性:pH对预处理和蛋白聚糖降解的影响。
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Expression of ADAMs ("a disintegrin and metalloprotease") in the human lung.
The metalloprotease-disintegrin ADAM8 contributes to temozolomide chemoresistance and enhanced invasiveness of human glioblastoma cells.金属蛋白酶-解整合素ADAM8促进替莫唑胺化疗耐药性及增强人胶质母细胞瘤细胞的侵袭性。
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ADAM-9 is a novel mediator of tenascin-C-stimulated invasiveness of brain tumor-initiating cells.ADAM-9是腱生蛋白-C刺激脑肿瘤起始细胞侵袭的一种新型介质。
Neuro Oncol. 2015 Aug;17(8):1095-105. doi: 10.1093/neuonc/nou362. Epub 2015 Feb 1.
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Expression of A disintegrin and metalloprotease 8 is associated with cell growth and poor survival in colorectal cancer.解整合素金属蛋白酶8的表达与结直肠癌的细胞生长及不良预后相关。
BMC Cancer. 2014 Aug 7;14:568. doi: 10.1186/1471-2407-14-568.
6
Oncogenic reg IV is a novel prognostic marker for glioma patient survival.致癌基因 reg IV 是一种新的胶质母细胞瘤患者生存预后标志物。
Diagn Pathol. 2012 Jun 19;7:69. doi: 10.1186/1746-1596-7-69.
“解整合素金属蛋白酶”(ADAMs)在人肺中的表达。
Virchows Arch. 2009 Apr;454(4):441-9. doi: 10.1007/s00428-009-0748-4. Epub 2009 Mar 3.
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Hypoxia-dependent expression of ADAM8 in human pancreatic cancer cell lines.人胰腺癌细胞系中ADAM8的缺氧依赖性表达
Exp Oncol. 2008 Jun;30(2):129-32.
5
ADAM8 expression is associated with increased invasiveness and reduced patient survival in pancreatic cancer.ADAM8的表达与胰腺癌侵袭性增加及患者生存率降低相关。
J Cell Mol Med. 2007 Sep-Oct;11(5):1162-74. doi: 10.1111/j.1582-4934.2007.00082.x.
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The 2007 WHO classification of tumours of the central nervous system.2007年世界卫生组织中枢神经系统肿瘤分类
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Metalloproteinase disintegrins ADAM8 and ADAM19 are highly regulated in human primary brain tumors and their expression levels and activities are associated with invasiveness.金属蛋白酶解整合素ADAM8和ADAM19在人类原发性脑肿瘤中受到高度调控,它们的表达水平和活性与侵袭性相关。
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Epidemiology and etiology of gliomas.胶质瘤的流行病学与病因学
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