Profiling Protein Markers Associated with Lymph Node Metastasis in Prostate Cancer by DIGE-based Proteomics Analysis
Profiling Protein Markers Associated with Lymph Node Metastasis in Prostate Cancer by DIGE-based Proteomics Analysis
复制标题
通过基于 DIGE 的蛋白质组学分析分析与前列腺癌淋巴结转移相关的蛋白质标记
DOI：
10.1021/pr900953s
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发表时间：
2010-01-01
影响因子：
4.4
通讯作者：
Gao, Xin
中科院分区：
文献类型：
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作者：
Pang, Jun;Liu, Wei-Peng;Gao, Xin
目前的预测工具和成像方式对于淋巴结转移性前列腺癌（LNM PCa）的术前诊断不够准确。引入蛋白质组学分析来筛选用于早期检测LNM PCa的潜在生物标志物。在我们的初步研究中，蛋白质样本本地化和LNM PCa以及良性前列腺增生组织进行了分析，使用二维荧光差异凝胶电泳（2-D DIGE）结合MALDI-TOF/TOF MS。我们确定了58个蛋白质差异表达的LNM PCa组相对于本地化PCa组。这些蛋白质中的六种，e-FABP 5、MCCC 2、PPA 2、Ezrin、SLP 2和SM 22，在功能上与癌症转移相关。因此，使用真实的时间PCR、蛋白质印迹和免疫组织化学染色，在来自原始队列以及来自更大的独立患者队列的组织样品中进一步验证了这些蛋白质的表达。此外，还通过ELISA检测了血清中e-FABP 5的水平。相对于局部PCa组织，LNM PCa组织具有增加的e-FABP 5、MCCC 2、PPA 2、Ezrin和SLP 2的表达和减少的SM 22的表达。LNM PCa患者血清e-FABP 5水平显著升高。本研究提供了证据表明，e-FABP 5、MCCC 2、PPA 2、Ezrin和SLP 2的表达增加以及SM 22的表达减少是LNM PCa存在的有用诊断标志物。
Current predictive tools and imaging modalities are not accurate enough for preoperative diagnosis of lymph node metastatic prostate cancer (LNM PCa). Proteomic analysis is introduced to screen potential biomarkers for early detection of LNM PCa. In our initial study, protein samples from localized and LNM PCa as well as benign prostatic hyperplasia tissues were analyzed using two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) coupled with MALDI-TOF/TOF MS. We identified 58 proteins that were differentially expressed in the LNM PCa group relative to the localized PCa group. Six of these proteins, e-FABP5, MCCC2, PPA2, Ezrin, SLP2, and SM22, are functionally relevant to cancer metastasis. Expression of these proteins was therefore further validated in tissue samples from the original cohort and also from a larger, independent cohort of patients using real time PCR, Western blotting, and immunohistochemistry staining. In addition, the serum levels of e-FABP5 were also examined by ELISA. Relative to localized PCa tissues, LNM PCa tissues had increased expression of e-FABP5, MCCC2, PPA2, Ezrin, and SLP2 and decreased expression of SM22. Patients with LNM PCa had significantly higher levels of serum e-FABP5. This study presents evidence that increased expression of e-FABP5, MCCC2, PPA2, Ezrin, and SLP2 and decreased expression of SM22 are useful diagnostic markers for the existence of LNM PCa.