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使用胺特异性等压标记(iTRAQ)结合二维液相色谱和串联质谱法在临床组织标本中寻找前列腺癌诊断、预后和治疗的潜在标志物。

Search for potential markers for prostate cancer diagnosis, prognosis and treatment in clinical tissue specimens using amine-specific isobaric tagging (iTRAQ) with two-dimensional liquid chromatography and tandem mass spectrometry.

作者信息

Garbis Spiros D, Tyritzis Stavros I, Roumeliotis Theodoros, Zerefos Panagiotis, Giannopoulou Eugenia G, Vlahou Antonia, Kossida Sophia, Diaz Jose, Vourekas Stavros, Tamvakopoulos Constantin, Pavlakis Kitty, Sanoudou Despina, Constantinides Constantinos A

机构信息

Biomedical Research Foundation, Academy of Athens, Greece.

出版信息

J Proteome Res. 2008 Aug;7(8):3146-58. doi: 10.1021/pr800060r. Epub 2008 Jun 14.

Abstract

This study aimed to identify candidate new diagnosis and prognosis markers and medicinal targets of prostate cancer (PCa), using state of the art proteomics. A total of 20 prostate tissue specimens from 10 patients with benign prostatic hyperplasia (BPH) and 10 with PCa (Tumour Node Metastasis [TNM] stage T1-T3) were analyzed by isobaric stable isotope labeling (iTRAQ) and two-dimensional liquid chromatography-tandem mass spectrometry (2DLC-MS/MS) approaches using a hybrid quadrupole time-of-flight system (QqTOF). The study resulted in the reproducible identification of 825 nonredundant gene products (p < or = 0.05) of which 30 exhibited up-regulation (> or =2-fold) and another 35 exhibited down-regulation (< or =0.5-fold) between the BPH and PCa specimens constituting a major contribution toward their global proteomic assessment. Selected findings were confirmed by immunohistochemical analysis of prostate tissue specimens. The proteins determined support existing knowledge and uncover novel and promising PCa biomarkers. The PCa proteome found can serve as a useful aid for the identification of improved diagnostic and prognostic markers and ultimately novel chemopreventive and therapeutic targets.

摘要

本研究旨在利用先进的蛋白质组学技术,鉴定前列腺癌(PCa)的新型诊断和预后标志物以及药物靶点。采用等压稳定同位素标记(iTRAQ)和二维液相色谱 - 串联质谱(2DLC - MS/MS)方法,使用混合四极杆飞行时间系统(QqTOF),对10例良性前列腺增生(BPH)患者和10例PCa患者(肿瘤淋巴结转移[TNM]分期为T1 - T3)的20份前列腺组织标本进行了分析。该研究可重复鉴定出825种非冗余基因产物(p≤0.05),其中30种在BPH和PCa标本之间表现出上调(≥2倍),另外35种表现出下调(≤0.5倍),这对它们的整体蛋白质组评估有重要贡献。通过对前列腺组织标本的免疫组化分析,证实了部分选定的研究结果。所确定的蛋白质支持现有知识,并揭示了新的、有前景的PCa生物标志物。所发现的PCa蛋白质组可为鉴定改进的诊断和预后标志物以及最终的新型化学预防和治疗靶点提供有用帮助。

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