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系统分析乳腺癌相关钙黏蛋白的表达水平与预后。

Systemic analysis of the expression levels and prognosis of breast cancer-related cadherins.

机构信息

Basic Medical College.

Medical Imaging Institute.

出版信息

Exp Biol Med (Maywood). 2021 Aug;246(15):1706-1720. doi: 10.1177/15353702211010417. Epub 2021 Apr 25.

Abstract

Cadherins form connection between cells, facilitate communication, and serve as essential agents in the progression of multiple cancers. Over 100 cadherins have been identified and they are mainly divided into four groups: classical cadherins (CDHs), protocadherins (PCDHs), desmosomal (DSC), and cadherin-related proteins. Accumulating evidence has indicated that several members of the cadherins are involved in breast cancer development. Nevertheless, the expression profiles and corresponding prognostic outcomes of these breast cancer-related cadherins are yet to be analyzed. Here, we examined the expression levels and prognostic potential of these breast cancer-related cadherins from the specific databases viz. oncomine, gene expression profiling interactive analysis, human protein atlas, UALCAN, Kaplan-Meier Plotter, and cBioPortal. We found that the CDH2/11 levels were higher in breast cancer tissues, compared to healthy breast tissues, whereas with CDH3-5, PCDH8/10, and DSC3, the levels were lower in the former than in the latter. Additionally, for CDH1/6/13/17/23, PCDH7, and FAT4, trancript level alterations between breast cancer and healthy tissues varied across different databases. The CDH1 protein levels were elevated in breast cancer tissues versus healthy breast tissues, whereas the protein levels of CDH3/11 and PCDH8/10 were reduced in breast cancer, compared to healthy breast tissues. For CDH15 and CDH23, the expression levels paralleled tumor stage. Survival analysis, using the Kaplan-Meier Plotter database, demonstrated that elevated CDH1-3 levels correlated with diminished relapse-free survival in breast cancer patients. Alternately, enhanced CDH4-6/15/17/23, PCDH10, DSC3, and FAT4 levels estimated a rise in relapse-free survival of breast cancer patients. These data suggest CDH1-3 to be a promising target for breast cancer precision therapy and CDH4-6/15/17/23, PCDH10, DSC3, and FAT4 to be novel biomarkers for breast cancer prognosis.

摘要

钙黏蛋白在细胞间形成连接,促进细胞间的通讯,是多种癌症进展的重要介质。目前已经鉴定出超过 100 种钙黏蛋白,主要分为四类:经典钙黏蛋白(classical cadherins,CDHs)、原钙黏蛋白(protocadherins,PCDHs)、桥粒钙黏蛋白(desmosomal cadherins,DSC)和钙黏蛋白相关蛋白。越来越多的证据表明,钙黏蛋白家族的几个成员参与了乳腺癌的发生发展。然而,这些与乳腺癌相关的钙黏蛋白的表达谱和相应的预后结果尚未得到分析。在这里,我们使用 Oncomine、基因表达谱交互分析、人类蛋白质图谱、UALCAN、Kaplan-Meier Plotter 和 cBioPortal 等特定数据库,检测了这些与乳腺癌相关的钙黏蛋白的表达水平和预后潜力。我们发现,与健康乳腺组织相比,乳腺癌组织中 CDH2/11 的水平更高,而 CDH3-5、PCDH8/10 和 DSC3 的水平则更低。此外,对于 CDH1/6/13/17/23、PCDH7 和 FAT4,不同数据库之间乳腺癌和健康组织的转录水平变化也不同。与健康乳腺组织相比,乳腺癌组织中 CDH1 蛋白水平升高,而 CDH3/11 和 PCDH8/10 蛋白水平降低。对于 CDH15 和 CDH23,表达水平与肿瘤分期平行。使用 Kaplan-Meier Plotter 数据库的生存分析表明,CDH1-3 水平升高与乳腺癌患者无复发生存率降低相关。相反,CDH4-6/15/17/23、PCDH10、DSC3 和 FAT4 水平升高预示着乳腺癌患者无复发生存率的提高。这些数据表明 CDH1-3 可能成为乳腺癌精准治疗的有前途的靶点,而 CDH4-6/15/17/23、PCDH10、DSC3 和 FAT4 可能成为乳腺癌预后的新的生物标志物。

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