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整合微阵列数据分析和靶向蛋白质组学进行生物标志物鉴定:在乳腺癌中的应用。

Integrating meta-analysis of microarray data and targeted proteomics for biomarker identification: application in breast cancer.

机构信息

Department of Laboratory Medicine and Pathobiology, University of Toronto , 1 King's College Circle, Toronto, ON M5S 1A8, Canada.

出版信息

J Proteome Res. 2014 Jun 6;13(6):2897-909. doi: 10.1021/pr500352e. Epub 2014 May 14.

Abstract

The development of signature biomarkers has gained considerable attention in the past decade. Although the most well-known examples of biomarker panels stem from gene expression studies, proteomic panels are becoming more relevant, with the advent of targeted mass spectrometry-based methodologies. At the same time, the development of multigene prognostic classifiers for early stage breast cancer patients has resulted in a wealth of publicly available gene expression data from thousands of breast cancer specimens. In the present study, we integrated transcriptome and proteome-based platforms to identify genes and proteins related to patient survival. Candidate biomarker proteins have been identified in a previously generated breast cancer tissue extract proteome. A mass-spectrometry-based assay was then developed for the simultaneous quantification of these 20 proteins in breast cancer tissue extracts. We quantified the relative expression levels of the 20 potential biomarkers in a cohort of 96 tissue samples from patients with early stage breast cancer. We identified two proteins, KPNA2 and CDK1, which showed potential to discriminate between estrogen receptor positive patients of high and low risk of disease recurrence. The role of these proteins in breast cancer prognosis warrants further investigation.

摘要

在过去的十年中,签名生物标志物的发展引起了相当大的关注。尽管最著名的生物标志物面板来自基因表达研究,但随着基于靶向质谱的方法的出现,蛋白质组学面板变得越来越相关。与此同时,用于早期乳腺癌患者的多基因预后分类器的开发导致了大量来自数千个乳腺癌标本的公开可用的基因表达数据。在本研究中,我们整合了基于转录组和蛋白质组的平台,以鉴定与患者生存相关的基因和蛋白质。在先前生成的乳腺癌组织提取物蛋白质组中已经鉴定出候选生物标志物蛋白。然后,开发了一种基于质谱的测定法,用于同时定量乳腺癌组织提取物中的这 20 种蛋白质。我们在 96 名早期乳腺癌患者的组织样本队列中定量了 20 种潜在生物标志物的相对表达水平。我们鉴定出两种蛋白,KPNA2 和 CDK1,它们具有区分雌激素受体阳性患者疾病复发高风险和低风险的潜力。这些蛋白质在乳腺癌预后中的作用值得进一步研究。

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