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[基于蛋白质组学的前列腺癌诊断和预后生物标志物]

[Proteome-based diagnostic and prognostic biomarkers of prostate cancer].

作者信息

Neuhaus J, Schiffer E, Siwy J, Mannello F, Horn L-C, Stolzenburg J-U

机构信息

Department für Operative Medizin, Klinik und Poliklinik für Urologie, Universitätsklinikum Leipzig AöR, Liebigstraße 20, 04103, Leipzig, Deutschland,

出版信息

Urologe A. 2013 Sep;52(9):1251-5. doi: 10.1007/s00120-013-3308-0.

DOI:10.1007/s00120-013-3308-0
PMID:24026060
Abstract

BACKGROUND

Due to comprehensive PSA screening, the incidence for prostate cancer (PCa) is rising. Therefore, there is an urgent need for improved PCa diagnostics and prognostic tools to differentiate between insignificant and aggressive, fast growing tumors.

METHODS

With the proteome-based method presented here, we were able to distinguish PCa from BPH, chronic prostatitis and healthy controls with 83 % sensitivity and 67 % specificity. Furthermore, the methods discerned advanced PCa from local, organ-confined PCa in a group of patients with gleason score 7 (80 % sensitivity, 82 % specificity).

RESULTS

Our proteomic approach is based on the analysis of low molecular weight polypeptides, identified as the endpoint of the naturally occuring liquefaction cascade in seminal plasma. For the first time using seminal plasma as a source, we analysed a complex network of interacting proteases and specific inhibitors, reflecting tumor biology specificity. Our diagnostic and prognostic tool is robust and easy to handle, and therefore it is well suitable for the laboratory and medical practice.

摘要

背景

由于全面的前列腺特异性抗原(PSA)筛查,前列腺癌(PCa)的发病率正在上升。因此,迫切需要改进PCa的诊断和预后工具,以区分无意义的和侵袭性的、快速生长的肿瘤。

方法

采用本文介绍的基于蛋白质组的方法,我们能够以83%的灵敏度和67%的特异性将PCa与良性前列腺增生(BPH)、慢性前列腺炎及健康对照区分开来。此外,该方法在一组Gleason评分为7分的患者中,能够从局限性、器官局限性PCa中辨别出晚期PCa(灵敏度80%,特异性82%)。

结果

我们的蛋白质组学方法基于对低分子量多肽的分析,这些多肽被确定为精浆中自然发生的液化级联反应的终产物。首次以精浆为来源,我们分析了一个由相互作用的蛋白酶和特异性抑制剂组成的复杂网络,反映了肿瘤生物学特异性。我们的诊断和预后工具稳健且易于操作,因此非常适合实验室和医学实践。

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本文引用的文献

1
Seminal plasma as a source of prostate cancer peptide biomarker candidates for detection of indolent and advanced disease.精浆作为前列腺癌肽生物标志物候选物的来源,用于检测惰性和进展性疾病。
PLoS One. 2013 Jun 24;8(6):e67514. doi: 10.1371/journal.pone.0067514. Print 2013.
2
Screening for prostate cancer.前列腺癌筛查
Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD004720. doi: 10.1002/14651858.CD004720.pub3.
3
Identification of differentially expressed proteins in direct expressed prostatic secretions of men with organ-confined versus extracapsular prostate cancer.
鉴定局限于前列腺内与前列腺外包膜侵犯前列腺癌患者直接前列腺分泌物中的差异表达蛋白。
Mol Cell Proteomics. 2012 Dec;11(12):1870-84. doi: 10.1074/mcp.M112.017889. Epub 2012 Sep 17.
4
Urinary proteome analysis for prostate cancer diagnosis: cost-effective application in routine clinical practice in Germany.用于前列腺癌诊断的尿蛋白质组分析:在德国常规临床实践中的具有成本效益的应用。
Int J Urol. 2012 Feb;19(2):118-25. doi: 10.1111/j.1442-2042.2011.02901.x. Epub 2011 Nov 22.
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Global cancer statistics.全球癌症统计数据。
CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4.
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Proteomics cataloging analysis of human expressed prostatic secretions reveals rich source of biomarker candidates.对人类前列腺分泌液进行蛋白质组编目分析,发现了丰富的生物标志物候选来源。
Proteomics Clin Appl. 2008 Apr 1;2(4):543-555. doi: 10.1002/prca.200780159.
7
Discovery and validation of urinary biomarkers for prostate cancer.前列腺癌尿液生物标志物的发现与验证
Proteomics Clin Appl. 2008 Mar 7;2(4):556-570. doi: 10.1002/prca.200780082.
8
Cancer statistics, 2009.2009年癌症统计数据。
CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. doi: 10.3322/caac.20006. Epub 2009 May 27.
9
Clinical collection and protein properties of expressed prostatic secretions as a source for biomarkers of prostatic disease.作为前列腺疾病生物标志物来源的前列腺分泌液的临床采集及蛋白质特性
J Proteomics. 2009 Aug 20;72(6):907-17. doi: 10.1016/j.jprot.2009.01.007. Epub 2009 Jan 20.
10
Evaluation of urine proteome pattern analysis for its potential to reflect coronary artery atherosclerosis in symptomatic patients.评估有症状患者尿液蛋白质组模式分析反映冠状动脉粥样硬化的潜力。
J Proteome Res. 2009 Jan;8(1):335-45. doi: 10.1021/pr800615t.