Evaluation and validation of MALDI-IMS in molecular pathology

基质辅助激光解吸电离成像质谱仪(MALDI-IMS)是一种相对较新的有效工具，可用于组织切片等复杂生物样品的分子分析。它已经在小患者和组织样本系列中展示了它的适用性和潜力。然而，它的稳健性和在大的患者系列上个性化用药的潜力的评价仍然缺乏。这项由四个在质谱学方面拥有特定背景知识和专长的互动且高度跨学科的研究小组共同发起的倡议旨在开发和应用新型离子(液体)基质用于MALDI-IMS，验证MALDI-IMS对四个大病例系列[胃癌(544例患者)、结肠癌(1500例患者)、胰腺癌(200例患者)和淀粉样变性(&gT；1500例患者)]的诊断、预后和预测能力，并了解微小微生物及其产品在健康皮肤以及红肿皮肤中的特定定位及其与上皮细胞宿主防御分子的相互作用。关于肿瘤学和淀粉样变性，我们希望检验以下假设和翻译方面：MALDI-IMS作为一项单一技术，能够从组织样本中提供相同数量的信息，例如三种单独技术的组合，即组织学、免疫组化和分子生物学；MALDI-IMS提供的生物标志物集能够提供与人类肿瘤的“传统”组织学分类相比更好的预后信息；MALDI-IMS可用于预测治疗反应；MALDI-IMS有助于淀粉样蛋白的诊断和分类；MALDI-IMS有助于监测治疗反应。关于粘膜完整性，我们希望验证这样的假设，即本土皮肤微生物通过以局部特异性的方式产生杀灭病原体的抗菌化合物而为宿主提供一些好处。生物标记物的识别和验证将是这些项目不可或缺的一部分。

Matrix-assisted laser desorption ionization-based imaging mass spectrometry (MALDI-IMS) is a relatively new and effective tool for the molecular analysis of complex biological samples such as tissue sections. It has demonstrated its applicability and potential on small patient and tissue sample series. However, vali-dation of its robustness and potential for personalized medicine on large patient series is still missing. This collaborative initiative of four interactive and highly interdisciplinary research groups with a specific background knowledge and expertise on mass spectrometry aims to exploit and apply novel ionic (liquid) matrices for MALDI-IMS, validate the diagnostic, prognostic and predictive capability of MALDI-IMS on four large patient series [gastric cancer (544 patients), colon cancer (>1500 patients), pancreatic cancer (>200 patients) and amyloidosis (>1500 patients)], and to understand the topospecific localization of mi-crobes, its products and its interaction with epithelial host defense molecules in healthy as well as in-flamed skin. With regard to oncology and amyloidosis we wish to test the following hypotheses and trans-lational aspects: MALDI-IMS as a single technology is able to provide the same amount of information from tissue samples like the combination of three separate techniques together, i.e. histology, immunohis-tochemistry and molecular biology; MALDI-IMS provides biomarker sets that are able to provide superior prognostic information compared with “conventional“ histological classification of human tumors; MALDI-IMS can be used to predict treatment response; MALDI-IMS facilitates the diagnosis and classification of amyloid; MALDI-IMS facilitates monitoring of therapy response. With regard to mucosal integrity we wish to test the hypotheses that indigenous skin microorganisms provide some benefit to the host by producing pathogen-killing antimicrobial compounds in a topospecific manner. Biomarker identification and valida-tion will be an integral part of these projects.