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[iTRAQ] 转移性肾细胞癌-iTRAQ

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发表于 2015-12-28 14:55:31 | 显示全部楼层 |阅读模式

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Mol Cell Proteomics. 2013 Jan;12(1):132-44. doi: 10.1074/mcp.M112.020701. Epub 2012 Oct 17.
Quantitative proteomic analysis in metastatic renal cell carcinoma reveals a unique set of proteins with potential prognostic significance.
IF=
14年6.564
13年7.254
12年7.251
11年7.398

研究关键词 转移性肾细胞癌,ITRAQ,Biobarker
研究概要:
    转移性肾细胞癌(RCC)是最难治疗的恶性肿瘤之一,RCC转移的分子标记物对评估RCC患者预后有重要的意义。本研究利用iTRAQ技术分析原发灶和和转移灶的蛋白表达差异,通过生物信息学分析选定可能可以作为肿瘤转移标记物的蛋白后,用免疫组化和western blot进行验证。本研究主要结论为Pfn1、14-3-3ζ和Gal-1蛋白在肿瘤中的高表达提示预后不良。对这些蛋白功能的进一步研究可能有助于发现新的RCC治疗靶点。本文技术路线如下:
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Abstract
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 identifyproteins 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 (14-3-3ζ), 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, 14-3-3ζ 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.
PMID: 23082029
免费全文链接
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536894/


Mol Cell Proteomics-2013-Masui-132-44.IF.7.251.pdf

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