Identification, prioritization, and evaluation of glycoproteins for aggressive prostate cancer using quantitative glycoproteomics and antibody-based assays on tissue specimens.

Identification, prioritization, and evaluation of glycoproteins for aggressive prostate cancer using quantitative glycoproteomics and antibody-based assays on tissue specimens.
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DOI:
10.1002/pmic.201200541
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发表时间:
2013-08
期刊:
影响因子:
3.4
通讯作者:
Zhang, Hui
Zhang, Hui
中科院分区:
生物学3区
文献类型:
--
作者:
Chen, Jing;Xi, Jiefeng;Tian, Yuan;Bova, George Steven;Zhang, Hui

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前列腺癌在性质上是高度异质性的;虽然大多数病例在临床上是不显著的,但有些病例是致命的。目前,对于侵袭性前列腺癌还没有可靠的筛查方法。由于大多数已建立的血清和尿液生物标志物是从患病组织分泌或泄漏的糖蛋白,因此目前的研究旨在使用组织标本鉴定侵袭性前列腺癌特异性的糖蛋白标志物。通过LC-MS/MS糖蛋白组学分析,我们鉴定了350种糖肽,其中17种在侵袭性前列腺癌中发生了改变。开发/购买ELISA测定法以在独立的组织组中评价4种候选物,即软骨寡聚基质蛋白(COMP)、骨膜蛋白、膜伯胺氧化酶(VAP-1)和组织蛋白酶L。与蛋白质组学分析一致,我们发现COMP和periostin表达在侵袭性前列腺肿瘤中显著增加,而VAP-1表达在侵袭性肿瘤中显著降低。此外,这些蛋白质在前列腺转移瘤中的表达也遵循蛋白质组学分析中观察到的相同模式。这项研究提供了一个工作流程,生物标志物的发现,优先级和评估侵略性前列腺癌标志物使用组织标本。我们的数据表明前列腺中COMP和骨膜蛋白的增加以及VAP-1表达的减少可能与侵袭性前列腺癌相关。
Prostate cancer is highly heterogeneous in nature; while the majority of cases are clinically insignificant, some cases are lethal. Currently, there are no reliable screening methods for aggressive prostate cancer. Since most established serum and urine biomarkers are glycoproteins secreted or leaked from the diseased tissue, the current study seeks to identify glycoprotein markers specific to aggressive prostate cancer using tissue specimens. With LC-MS/MS glycoproteomic analysis, we identified 350 glycopeptides with 17 being altered in aggressive prostate cancer. ELISA assays were developed/purchased to evaluate 4 candidates, i.e. cartilage oligomeric matrix protein (COMP), periostin, membrane primary amine oxidase (VAP-1) and cathepsin L, in independent tissue sets. In agreement with the proteomic analysis, we found that COMP and periostin expressions were significantly increased in aggressive prostate tumors while VAP-1 expression was significantly decreased in aggressive tumor. In addition, the expression of these proteins in prostate metastases also follows the same pattern observed in the proteomic analysis. This study provides a workflow for biomarker discovery, prioritization and evaluation of aggressive prostate cancer markers using tissue specimens. Our data suggest increase in COMP and periostin and decrease in VAP-1 expression in the prostate may be associated with aggressive prostate cancer.
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