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基质辅助激光解吸电离成像质谱法利用大规模组织微阵列揭示结直肠癌中多个临床相关的肿块。

MALDI imaging mass spectrometry reveals multiple clinically relevant masses in colorectal cancer using large-scale tissue microarrays.

作者信息

Hinsch A, Buchholz M, Odinga S, Borkowski C, Koop C, Izbicki J R, Wurlitzer M, Krech T, Wilczak W, Steurer S, Jacobsen F, Burandt E-C, Stahl P, Simon R, Sauter G, Schlüter H

机构信息

Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

出版信息

J Mass Spectrom. 2017 Mar;52(3):165-173. doi: 10.1002/jms.3916.

Abstract

For identification of clinically relevant masses to predict status, grade, relapse and prognosis of colorectal cancer, we applied Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) to a tissue micro array containing formalin-fixed and paraffin-embedded tissue samples from 349 patients. Analysis of our MALDI-IMS data revealed 27 different m/z signals associated with epithelial structures. Comparison of these signals showed significant association with status, grade and Ki-67 labeling index. Fifteen out of 27 IMS signals revealed a significant association with survival. For seven signals (m/z 654, 776, 788, 904, 944, 975 and 1013) the absence and for eight signals (m/z 643, 678, 836, 886, 898, 1095, 1459 and 1477) the presence were associated with decreased life expectancy, including five masses (m/z 788, 836, 904, 944 and 1013) that provided prognostic information independently from the established prognosticators pT and pN. Combination of these five masses resulted in a three-step classifier that provided prognostic information superior to univariate analysis. In addition, a total of 19 masses were associated with tumor stage, grade, metastasis and cell proliferation. Our data demonstrate the suitability of combining IMS and large-scale tissue micro arrays to simultaneously identify and validate clinically useful molecular marker. Copyright © 2017 John Wiley & Sons, Ltd.

摘要

为了识别临床上相关的肿块以预测结直肠癌的状态、分级、复发和预后,我们将基质辅助激光解吸电离(MALDI)成像质谱(IMS)应用于一个组织微阵列,该阵列包含来自349例患者的福尔马林固定石蜡包埋组织样本。对我们的MALDI-IMS数据进行分析后发现,有27种不同的m/z信号与上皮结构相关。这些信号的比较显示与状态、分级和Ki-67标记指数有显著关联。27个IMS信号中有15个与生存率有显著关联。对于7个信号(m/z 654、776、788、904、944、975和1013),其缺失以及对于8个信号(m/z 643、678、836、886、898、1095、1459和1477),其存在与预期寿命缩短相关,其中包括5个肿块(m/z 788、836、904、944和1013),它们独立于已确立的预后指标pT和pN提供预后信息。这5个肿块的组合形成了一个三步分类器,其提供的预后信息优于单变量分析。此外,共有19个肿块与肿瘤分期、分级、转移和细胞增殖相关。我们的数据证明了将IMS与大规模组织微阵列相结合以同时识别和验证临床上有用的分子标志物的适用性。版权所有© 2017约翰威立父子有限公司。

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