LC-MS/MS Analysis of Differentially Expressed Glioblastoma Membrane Proteome Reveals Altered Calcium Signaling and Other Protein Groups of Regulatory Functions
LC-MS/MS Analysis of Differentially Expressed Glioblastoma Membrane Proteome Reveals Altered Calcium Signaling and Other Protein Groups of Regulatory Functions
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DOI：
10.1074/mcp.m111.013565
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发表时间：
2012-06-01
影响因子：
7
通讯作者：
Sirdeshmukh, Ravi
中科院分区：
文献类型：
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作者：
Polisetty, Ravindra Varma;Gautam, Poonam;Sirdeshmukh, Ravi
膜蛋白在癌症的发生和发展中起着关键作用。我们通过高分辨率LC-MS/MS质谱和iTRAQ定量研究了多形性胶质母细胞瘤（GBM）（最常见和最具侵袭性的原发性脑肿瘤类型）中差异表达的膜蛋白。共鉴定了1834种膜蛋白，具有高置信度，其中356种蛋白被发现改变了2倍或更多（198种上调和158种下调）;其中56%是已知的与主要细胞过程相关的膜蛋白。通过免疫组织化学确认了单个标本上代表性蛋白质的质谱结果。在将差异表达的蛋白质映射到细胞途径和功能网络时，我们特别观察到许多钙结合蛋白被改变，暗示GBM中钙信号传导和稳态的失调，在该报告中也发现一种途径被富集（Dong，H.，罗湖，加-地洪，S.，萧，H.，肖，Y.，金，L.，陈，R.，和Xiong，M.（2010）胶质母细胞瘤中突变、miRNA和mRNA表达的综合分析。4，163）基于GBM的癌症基因组图谱分析。我们用癌症基因组图谱转录组数据集鉴定的356种蛋白质的注释表明与295种相应的转录本重叠，其中包括49种潜在的miRNA靶点;许多转录本与蛋白质的表达状态相关。近50%的差异表达蛋白可归类为跨膜结构域或信号序列蛋白（159/356），可能出现在脑脊液或血浆中。有趣的是，其中75个已经在正常脑脊液或血浆中与其他蛋白质一起沿着被报道。GBM差异表达膜蛋白质组的首次深入分析证实了早期研究中涉及的基因/蛋白质，并揭示了GBM或任何其他癌症中首次报道的新候选物，这些候选物可以进一步研究用于临床应用。Molecular & Cellular Proteomics 11：10.1074/mcp. M111.013565，1-15，2012.
Membrane proteins play key roles in the development and progression of cancer. We have studied differentially expressed membrane proteins in glioblastoma multiforme (GBM), the most common and aggressive type of primary brain tumor, by high resolution LC-MS/MS mass spectrometry and quantitation by iTRAQ. A total of 1834 membrane proteins were identified with high confidence, of which 356 proteins were found to be altered by 2-fold change or more (198 up- and 158 down-regulated); 56% of them are known membrane proteins associated with major cellular processes. Mass spectrometry results were confirmed for representative proteins on individual specimens by immunohistochemistry. On mapping of the differentially expressed proteins to cellular pathways and functional networks, we notably observed many calcium-binding proteins to be altered, implicating deregulation of calcium signaling and homeostasis in GBM, a pathway also found to be enriched in the report (Dong, H., Luo, L., Hong, S., Siu, H., Xiao, Y., Jin, L., Chen, R., and Xiong, M. (2010) Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma. BMC Syst. Biol. 4, 163) based on The Cancer Genome Atlas analysis of GBMs. Annotations of the 356 proteins identified by us with The Cancer Genome Atlas transcriptome data set indicated overlap with 295 corresponding transcripts, which included 49 potential miRNA targets; many transcripts correlated with proteins in their expression status. Nearly 50% of the differentially expressed proteins could be classified as transmembrane domain or signal sequence-containing proteins (159 of 356) with potential of appearance in cerebrospinal fluid or plasma. Interestingly, 75 of them have been already reported in normal cerebrospinal fluid or plasma along with other proteins. This first, in-depth analysis of the differentially expressed membrane proteome of GBM confirms genes/proteins that have been implicated in earlier studies, as well as reveals novel candidates that are being reported for the first time in GBM or any other cancer that could be investigated further for clinical applications. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.013565, 1-15, 2012.