前列腺癌的综合基因组和蛋白质组分析揭示了转移进展的特征。

Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression.

作者信息

Varambally Sooryanarayana, Yu Jianjun, Laxman Bharathi, Rhodes Daniel R, Mehra Rohit, Tomlins Scott A, Shah Rajal B, Chandran Uma, Monzon Federico A, Becich Michael J, Wei John T, Pienta Kenneth J, Ghosh Debashis, Rubin Mark A, Chinnaiyan Arul M

机构信息

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.

出版信息

Cancer Cell. 2005 Nov;8(5):393-406. doi: 10.1016/j.ccr.2005.10.001.

DOI:10.1016/j.ccr.2005.10.001

PMID:16286247

Abstract

Molecular profiling of cancer at the transcript level has become routine. Large-scale analysis of proteomic alterations during cancer progression has been a more daunting task. Here, we employed high-throughput immunoblotting in order to interrogate tissue extracts derived from prostate cancer. We identified 64 proteins that were altered in prostate cancer relative to benign prostate and 156 additional proteins that were altered in metastatic disease. An integrative analysis of this compendium of proteomic alterations and transcriptomic data was performed, revealing only 48%-64% concordance between protein and transcript levels. Importantly, differential proteomic alterations between metastatic and clinically localized prostate cancer that mapped concordantly to gene transcripts served as predictors of clinical outcome in prostate cancer as well as other solid tumors.

摘要

在转录水平对癌症进行分子特征分析已成为常规操作。对癌症进展过程中蛋白质组改变进行大规模分析一直是一项更具挑战性的任务。在此，我们采用高通量免疫印迹法来研究源自前列腺癌的组织提取物。我们鉴定出64种相对于良性前列腺组织在前列腺癌中发生改变的蛋白质，以及另外156种在转移性疾病中发生改变的蛋白质。对这一蛋白质组改变和转录组数据的汇总进行了综合分析，结果显示蛋白质水平与转录水平之间的一致性仅为48% - 64%。重要的是，转移性前列腺癌与临床局限性前列腺癌之间蛋白质组的差异改变，若与基因转录本一致，则可作为前列腺癌以及其他实体瘤临床结局的预测指标。