Imaging Mass Spectrometry of a Specific Fragment of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase Kinase 2 Discriminates Cancer from Uninvolved Prostate Tissue
Imaging Mass Spectrometry of a Specific Fragment of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase Kinase 2 Discriminates Cancer from Uninvolved Prostate Tissue
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DOI：
10.1158/1078-0432.ccr-08-2892
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发表时间：
2009-09-01
影响因子：
11.5
通讯作者：
Semmes, O. John
中科院分区：
文献类型：
--
作者：
Cazares, Lisa H.;Troyer, Dean;Semmes, O. John
目的：组织病理学是组织诊断的标准方法和病理学的核心。虽然目前的系统提供了预后信息，有必要的分子标记，提高诊断和更好地预测临床预后。定位活检组织中疾病特异性分子变化的能力将有助于改善关键病理学决策。使用基质辅助激光解吸/电离成像质谱法从组织中的蛋白质的直接分析有可能补充形态学与潜在的molecular detail.Experimental Design：一个发现集的11个前列腺癌（PCa），含10个良性前列腺组织切片进行了蛋白质表达差异的评价。使用54个组织切片（23个PCa和31个良性）的单独验证集来验证结果。进行冷冻切片以产生由病理学家分析的组织切片，以确定组织形态和用于成像质谱的镜像切片。光谱采集和信号的强度被绘制为一个功能的位置在tissue.Results：一个表达谱被发现，PCa和正常组织之间的区别。在m/z4，355处的单个离子的过表达能够区分癌症与未涉及的组织。串联质谱鉴定该标记物为促分裂原活化蛋白激酶/细胞外信号调节激酶2（MEKK 2）的片段。MEKK 2区分肿瘤与正常细胞的能力是正交confirmed.Conclusions：这项研究强调了这种方法的潜力，发现分子的细节，可以与病理决策。此外，MEKK 2的鉴定显示了发现与PCa生物学相关的蛋白质的能力。(Clin Cancer Res 2009;15（17）：5541-51）
Purpose: Histopathology is the standard approach for tissue diagnostics and center-piece of pathology. Although the current system provides prognostic information, there is need for molecular markers that enhance diagnosis and better predict clinical prognosis. The ability to localize disease-specific molecular changes in biopsy tissue would help improve critical pathology decision making. Direct profiling of proteins from tissue using matrix-assisted laser desorption/ionization imaging mass spectrometry has the potential to supplement morphology with underlying molecular detail.Experimental Design: A discovery set of 11 prostate cancer (PCa)-containing and 10 benign prostate tissue sections was evaluated for protein expression differences. A separate validation set of 54 tissue sections (23 PCa and 31 benign) was used to verify the results. Cryosectioning was done to yield tissue sections analyzed by a pathologist to determine tissue morphology and mirror sections for imaging mass spectrometry. Spectra were acquired and the intensity of signals was plotted as a function of the location within the tissue.Results: An expression profile was found that discriminates between PCa and normal tissue. The overexpression of a single ion at m/z4,355 was able to discriminate cancer from uninvolved tissue. Tandem mass spectrometry identified this marker as a fragment of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 2 (MEKK2). The ability of MEKK2 to discriminate tumor from normal cells was orthogonally confirmed.Conclusions: This study highlights the potential of this approach to uncover molecular detail that can be correlated with pathology decision making. In addition, the identification of MEKK2 shows the ability to discover proteins of relevance to PCa biology. (Clin Cancer Res 2009;15(17):5541-51)