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在福尔马林固定和石蜡包埋的乳腺癌组织中分析信号通路,揭示了 EGFR、HER2、HER3 和 uPAR 之间的串扰。

Profiling signalling pathways in formalin-fixed and paraffin-embedded breast cancer tissues reveals cross-talk between EGFR, HER2, HER3 and uPAR.

机构信息

Institute of Pathology, Technische Universität Muenchen, Munich, Germany.

出版信息

J Cell Physiol. 2012 Jan;227(1):204-12. doi: 10.1002/jcp.22718.

DOI:10.1002/jcp.22718
PMID:21391216
Abstract

In the last few years, new approaches and developments in patient-tailored cancer therapies have raised the need to select, more precisely, those patients who will respond to personalized treatments. Therefore, the most efficient way for optimal therapy and patient selection is to provide a tumour-specific protein network portrait prior to treatment. The aim of our study was to monitor protein networks in formalin-fixed and paraffin-embedded (FFPE) breast cancer tissues, with special emphasis on epidermal growth factor receptor 2 (HER2)-mediated signalling pathways, to identify and validate new disease markers. For this purpose we used a recently developed technology to extract full-length proteins from FFPE tissues and analysed 23 molecules involved in HER2-related signalling by reverse phase protein microarray (RPPA) in a series of 106 FFPE breast cancer tissue samples. We found a significant correlation of HER2 with human epidermal growth factor receptor 3 (HER3/erbB3), epidermal growth factor receptor 1 (EGFR/HER1/erbB1) and urokinase plasminogen receptor (uPAR) in routinely used FFPE breast cancer tissues. Thus, targeting HER2, EGFR, HER3 and uPAR together may offer a more efficient treatment option for patients with breast cancer.

摘要

在过去的几年中,针对患者的癌症治疗新方法和新进展提出了需要更准确地选择那些对个性化治疗有反应的患者。因此,为了实现最佳治疗和患者选择,最有效的方法是在治疗前提供肿瘤特异性蛋白质网络图谱。我们的研究目的是监测福尔马林固定和石蜡包埋(FFPE)乳腺癌组织中的蛋白质网络,特别强调表皮生长因子受体 2(HER2)介导的信号通路,以鉴定和验证新的疾病标志物。为此,我们使用了一种新开发的技术从 FFPE 组织中提取全长蛋白质,并通过反向蛋白质微阵列(RPPA)分析了 106 例 FFPE 乳腺癌组织样本中涉及 HER2 相关信号通路的 23 种分子。我们发现,在常规使用的 FFPE 乳腺癌组织中,HER2 与人类表皮生长因子受体 3(HER3/erbB3)、表皮生长因子受体 1(EGFR/HER1/erbB1)和尿激酶型纤溶酶原激活物受体(uPAR)之间存在显著相关性。因此,针对 HER2、EGFR、HER3 和 uPAR 一起治疗可能为乳腺癌患者提供更有效的治疗选择。

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Profiling signalling pathways in formalin-fixed and paraffin-embedded breast cancer tissues reveals cross-talk between EGFR, HER2, HER3 and uPAR.在福尔马林固定和石蜡包埋的乳腺癌组织中分析信号通路,揭示了 EGFR、HER2、HER3 和 uPAR 之间的串扰。
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