Periostin identified as a potential biomarker of prostate cancer by iTRAQ-proteomics analysis of prostate biopsy.
Periostin identified as a potential biomarker of prostate cancer by iTRAQ-proteomics analysis of prostate biopsy.
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DOI：
10.1186/1477-5956-9-22
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发表时间：
2011-04-19
期刊：
影响因子：
2
通讯作者：
Ding Q
中科院分区：
文献类型：
--
作者：
Sun C;Song C;Ma Z;Xu K;Zhang Y;Jin H;Tong S;Ding W;Xia G;Ding Q
蛋白质组学可以帮助我们更好地了解参与前列腺癌（PCa）发生和发展的多种蛋白质的变化，并确定更多的诊断和预后生物标志物。本研究的目的是通过蛋白质组学分析，使用同量异位素标签的相对和绝对定量（iTRAQ）筛选前列腺癌的生物标志物。根据病理结果将行前列腺穿刺活检的患者分为3组：良性前列腺增生（BPH，n = 20）、前列腺癌（PCa，n = 20）和BPH伴局部前列腺上皮内瘤变（PIN，n = 10）。采用iTRAQ和二维液相色谱-串联质谱（2DLC-MS/MS）对所有患者的标本进行分析。用MetaCore软件分析差异表达基因的GO功能和转录调控网络。Western blotting和免疫组化染色分析目的蛋白。从13787个不同的肽中共鉴定出760个蛋白质，包括两种具有临床应用价值的常见蛋白质：前列腺特异性抗原（PSA）和前列腺酸性磷酸酶（PAP）。进一步分析PCa组与BPH组差异表达的蛋白质。与BPH相比，20个蛋白质在PCa中显著上调（>1.5倍），而26个蛋白质在PCa中显著下调（<0.66倍）。根据GO数据库，将差异表达蛋白分为3类：细胞组分（CC）、分子功能（MF）和生物过程（BP）。差异表达蛋白的前5位转录调控网络分别通过激活SP 1、p53、YY 1、雄激素受体（AR）和c-Myc启动。我们的研究表明，iTRAQ技术是一种新的策略，全球蛋白质组学分析的PCa组织。与BPH相比，PCa中骨膜蛋白的显著上调不仅可以为PCa预后的有希望的生物标志物提供线索，而且可以为治疗干预提供潜在靶点。
Proteomics may help us better understand the changes of multiple proteins involved in oncogenesis and progression of prostate cancer(PCa) and identify more diagnostic and prognostic biomarkers. The aim of this study was to screen biomarkers of PCa by the proteomics analysis using isobaric tags for relative and absolute quantification(iTRAQ). The patients undergoing prostate biopsies were classified into 3 groups according to pathological results: benign prostate hyperplasia (BPH, n = 20), PCa(n = 20) and BPH with local prostatic intraepithelial neoplasm(PIN, n = 10). Then, all the specimens from these patients were analyzed by iTRAQ and two-dimensional liquid chromatography-tandem mass spectrometry (2DLC-MS/MS). The Gene Ontology(GO) function and the transcription regulation networks of the differentially expressed were analyzed by MetaCore software. Western blotting and Immunohistochemical staining were used to analyze the interesting proteins. A total of 760 proteins were identified from 13787 distinct peptides, including two common proteins that enjoy clinical application: prostate specific antigen (PSA) and prostatic acid phosphatase(PAP). Proteins that expressed differentially between PCa and BPH group were further analyzed. Compared with BPH, 20 proteins were significantly differentially up-regulated (>1.5-fold) while 26 were significantly down-regulated in PCa(<0.66-fold). In term of GO database, the differentially expressed proteins were divided into 3 categories: cellular component(CC), molecular function (MF) and biological process(BP). The top 5 transcription regulation networks of the differentially expressed proteins were initiated through activation of SP1, p53, YY1, androgen receptor(AR) and c-Myc The overexpression of periostin in PCa was verified by western blotting and immunohistochemical staining. Our study indicates that the iTRAQ technology is a new strategy for global proteomics analysis of the tissues of PCa. A significant up-regulation of periostin in PCa compared to BPH may provide clues for not only a promising biomarker for the prognosis of PCa but also a potential target for therapeutical intervention.
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