MALDI imaging mass spectrometry reveals COX7A2, TAGLN2 and S100-A10 as novel prognostic markers in Barrett's adenocarcinoma

MALDI imaging mass spectrometry reveals COX7A2, TAGLN2 and S100-A10 as novel prognostic markers in Barrett's adenocarcinoma
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DOI:
10.1016/j.jprot.2012.02.012
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发表时间:
2012-08-03
影响因子:
3.3
通讯作者:
Walch, Axel
Walch, Axel
中科院分区:
生物学2区
文献类型:
--
作者:
Elsner, Mareike;Rauser, Sandra;Walch, Axel

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为了表征在巴雷特腺癌及其癌前阶段中发现的蛋白质组变化,通过MALDI成像MS分析组织学上定义的前体和浸润性癌病变的蛋白质组学谱。对于主要蛋白质组学筛选,使用38个新鲜冷冻巴雷特腺癌患者组织样本的发现队列。其目标是找到可能用作监测癌症发展以及预测区域淋巴结转移和疾病结果的标志物的蛋白质。使用质谱法进行蛋白质鉴定,并通过免疫组织化学在独立的验证组上验证结果,我们可以鉴定巴雷特腺癌和前体病变之间60种差异表达的m/z种类中的两种:COX 7A 2和S100-A10。此外,在具有和不具有区域淋巴结转移的巴雷特腺癌病例中差异表达的22种m/z物种中,一种被鉴定为TAGLN 2。在验证集中,我们发现COX 7A 2和TAGLN 2的表达水平与预后不良相关,而S100-A10通过多变量分析被证实为Barrett腺癌中的新的独立预后因素。我们的研究结果强调了MALDI成像的高潜力,揭示新的生物学意义的分子细节,从癌症组织,可能有潜在的临床应用。这篇文章是一个特殊问题的一部分,题为:翻译蛋白质组学。(C)2012爱思唯尔有限公司版权所有。
To characterize proteomic changes found in Barrett's adenocarcinoma and its premalignant stages, the proteomic profiles of histologically defined precursor and invasive carcinoma lesions were analyzed by MALDI imaging MS. For a primary proteomic screening, a discovery cohort of 38 fresh frozen Barrett's adenocarcinoma patient tissue samples was used. The goal was to find proteins that might be used as markers for monitoring cancer development as well as for predicting regional lymph node metastasis and disease outcome. using mass spectrometry for protein identification and validating the results by immunohistochemistry on an independent validation set, we could identify two of 60 differentially expressed m/z species between Barrett's adenocarcinoma and the precursor lesion: COX7A2 and S100-A10. Furthermore, among 22 m/z species that are differentially expressed in Barrett's adenocarcinoma cases with and without regional lymph node metastasis, one was identified as TAGLN2. In the validation set, we found a correlation of the expression levels of COX7A2 and TAGLN2 with a poor prognosis while S100-A10 was confirmed by multivariate analysis as a novel independent prognostic factor in Barrett's adenocarcinoma. Our results underscore the high potential of MALDI imaging for revealing new biologically significant molecular details from cancer tissues which might have potential for clinical application. This article is part of a Special Issue entitled: Translational Proteomics. (C) 2012 Elsevier B.V. All rights reserved.