Background:Mass spectrometry imaging (MSI) lipidomics is a subset of spatially resolved techniques wherein lipids are detected by mass spectrometry, allowing their multiplexed detection and acquiring position-correlated spectra along a tissue section. Rapid advances in the field provide solid evidence demonstrating how specific and regulated lipid distribution is in any biological context.Objectives: Herein, we describe the MSI, particularly matrix-assisted laser desorption/ionization (MALDI-MSI), challenges and advantages in defining human lung pathophysiology, particularly in lung cancer and chronic obstructive pulmonary disease, leading causes of death.Methods: MALDI-MSI analysis of lung tissue sections at 25 μm of lateral resolution allowed associating specific lipid profiles with the main tissues present and independently assessing the impact on lipid composition of smoking, chronic inflammation, and lung cancer.Results: Consistent with MALDI-MSI studies in tumor epithelia, arachidonic acid-containing phospholipids increased, agreeing with its role as a precursor of numerous bioactive molecules participating in cell differentiation and malignization. Next, a gene expression dataset of epithelial human non-small cell lung cancer samples was analyzed using system biology approaches, revealing that, consistent with the most relevant changes in lipid profiles, the network dominated by the tumor-associated module included genes tightly involved in phosphatidylinositol and sphingolipid metabolism. Hence, despite the intrinsic difficulties entailed by lung tissue handling, the results strongly encourage future analysis at higher lateral resolutions so that the lipidome changes associated with each lung cellular type, even subtype, could be fully mapped. Therefore, MALDI-MSI lipidomics definitively broadens the options, some still rather unexplored, to delve into pathophysiology at the cell-type level.
背景：质谱成像脂质组学是空间分辨技术的一个分支，通过质谱检测脂质，实现脂质的多重检测并获取沿组织切片的空间关联谱图。该领域的快速发展为揭示脂质在各类生物环境中的特异性与调控性分布提供了坚实证据。 目的：本文重点阐述质谱成像技术，特别是基质辅助激光解吸/电离质谱成像在解析人类肺部病理生理机制中的应用挑战与优势，重点关注肺癌和慢性阻塞性肺疾病这两种主要致死性疾病。 方法：通过25微米横向分辨率的MALDI-MSI对肺组织切片进行分析，将特定脂质谱与主要组织类型建立关联，并独立评估吸烟、慢性炎症及肺癌对脂质组成的影响。 结果：与肿瘤上皮组织的MALDI-MSI研究结果一致，含花生四烯酸的磷脂含量显著升高，这与其作为参与细胞分化和恶性转化的多种生物活性分子前体的作用相符。进一步通过系统生物学方法分析人类非小细胞肺癌上皮样本的基因表达数据集发现，与脂质谱最显著变化相呼应的是，肿瘤相关模块主导的调控网络包含与磷脂酰肌醇及鞘脂代谢密切相关的基因。尽管肺组织处理存在固有困难，本研究结果仍强烈支持未来采用更高横向分辨率进行分析，以全面绘制与各肺细胞类型（乃至亚型）相关的脂质组变化图谱。 结论：MALDI-MSI脂质组学技术显著拓展了在细胞类型层面探究病理生理机制的途径，其中部分方向仍具有广阔的探索空间。
肿瘤(癌症)患者之家