Evaluation and validation of MALDI-IMS in molecular pathology

基于基质辅助激光解吸电离成像质谱法（MALDI-IMS）是一种相对较新的有效工具，用于复杂生物样品（如组织切片）的分子分析。该方法在小型患者和组织样品系列上的适用性和潜力得到了验证。然而，其稳健性和在大型患者系列中个性化医疗的潜力的验证仍然缺失。该合作计划由四个具有质谱特定背景知识和专业知识的互动性和高度跨学科的研究小组组成，旨在开发和应用MALDI-IMS的新型离子（液体）基质，验证MALDI-IMS对四大患者系列（胃癌（544例）、结肠癌（1500例）、胰腺癌（200例）和淀粉样变性（1500例））的诊断、预后和预测能力。了解健康皮肤和炎症皮肤中微袍及其产物的拓扑特异性定位及其与上皮宿主防御分子的相互作用。关于肿瘤学和淀粉样变性，我们希望测试以下假设和转化方面：MALDI-IMS作为一种单一技术能够从组织样本中提供相同数量的信息，就像三种独立技术的组合一样，即组织学，免疫化学和分子生物学；与“传统”的人类肿瘤组织学分类相比，MALDI-IMS提供的生物标志物集能够提供更好的预后信息；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，我们希望测试的假设，本地皮肤微生物提供一些有益的宿主通过生产病原体杀灭抗菌化合物在一个特定的方式。生物标记物的鉴定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.