Quantitative Proteomic Analysis in Metastatic Renal Cell Carcinoma Reveals a Unique Set of Proteins with Potential Prognostic Significance
Quantitative Proteomic Analysis in Metastatic Renal Cell Carcinoma Reveals a Unique Set of Proteins with Potential Prognostic Significance
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DOI：
10.1074/mcp.m112.020701
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发表时间：
2013-01-01
影响因子：
7
通讯作者：
Yousef, George M.
中科院分区：
文献类型：
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作者：
Masui, Olena;White, Nicole M. A.;Yousef, George M.
转移性肾细胞癌(RCC)是最耐药的恶性肿瘤之一，患者预后很差，五年生存率为10%。识别可以预测转移潜能的标志物将对改善患者的预后有很大的作用。在这项研究中，我们使用等压标记的差异蛋白质组学相对和绝对定量(ITRAQ)标记和LC-MS/MS分析来识别在转移性和原发肾细胞癌中差异表达的蛋白质。我们鉴定了1256个非冗余蛋白，并对其中的456个进行了定量。进一步分析发现29个蛋白在转移性和原发肾细胞癌中差异表达(12个过度表达，17个低表达)。通过Western印迹和免疫组织化学分析，证实Profilin-1(PFN1)、14-3-3Zeta/Delta(14-3-3xi)和Galectin-1(Gal-1)在两组独立的组织中表达异常。等级聚类分析表明，转移性肾癌特异的蛋白质表达谱可以区分侵袭性和非侵袭性肾癌。通路分析表明，异常蛋白参与了与肿瘤进展和转移相关的细胞过程。此外，使用一小组肿瘤的初步分析表明，PFN1表达增加与不良预后相关，是肾癌潜在的预后标志。此外，14-3-3xi和Gal-1在预后不良的肿瘤中的表达也高于预后良好的肿瘤。转移性肾癌中的蛋白表达异常是肾癌患者潜在的预后标志物，对其相关生物学途径的深入了解将为转移性肾癌靶向治疗的研究奠定基础。分子与细胞蛋白质组学12：10.1074/mcp.M112.020701,132-144,2013年。
Metastatic renal cell carcinoma (RCC) is one of the most treatment-resistant malignancies, and patients have a dismal prognosis, with a < 10% five-year survival rate. The identification of markers that can predict the potential for metastases will have a great effect in improving patient outcomes. In this study, we used differential proteomics with isobaric tags for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to identify proteins that are differentially expressed in metastatic and primary RCC. We identified 1256 non-redundant proteins, and 456 of these were quantified. Further analysis identified 29 proteins that were differentially expressed (12 overexpressed and 17 underexpressed) in metastatic and primary RCC. Dysregulated protein expressions of profilin-1 (Pfn1), 14-3-3 zeta/delta (14-3-3 xi), and galectin-1 (Gal-1) were verified on two independent sets of tissues by means of Western blot and immunohistochemical analysis. Hierarchical clustering analysis showed that the protein expression profile specific for metastatic RCC can distinguish between aggressive and non-aggressive RCC. Pathway analysis showed that dysregulated proteins are involved in cellular processes related to tumor progression and metastasis. Furthermore, preliminary analysis using a small set of tumors showed that increased expression of Pfn1 is associated with poor outcome and is a potential prognostic marker in RCC. In addition, 14-3-3 xi and Gal-1 also showed higher expression in tumors with poor prognosis than in those with good prognosis. Dysregulated proteins in metastatic RCC represent potential prognostic markers for kidney cancer patients, and a greater understanding of their involved biological pathways can serve as the foundation of the development of novel targeted therapies for metastatic RCC. Molecular & Cellular Proteomics 12: 10.1074/mcp.M112.020701, 132-144, 2013.