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探索6-aza-2-thiothymine作为一种MALDI-MSI矩阵,用于形式素固定的对嵌入的临床样本的空间脂组学

Natalia Shelly Porto¹, Simone Serrao¹, Greta Bindi¹

¹Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy.

|August 27, 2025

概括

这项研究表明,6-aza-2-thiothymine (ATT) 是一种有效的矩阵,用于在甲固定嵌 (FFPE) 组织中对脂质进行矩阵辅助激光吸附/电离质谱成像 (MALDI-MSI). 在临床样本中进行详细的脂质映射,有助于疾病研究.

科学领域:

生物医学质谱
脂质组学
分子病理学

背景情况:

脂质在疾病的发病,进展和结果中起着关键作用.
矩阵辅助激光吸附/电离质谱成像 (MALDI-MSI) 可以直接从组织中进行空间分辨的脂质分析.
有效的MALDI矩阵选择对于在具有挑战性的样本中进行敏感脂质分析至关重要,例如固定甲嵌入 (FFPE) 组织.

研究的目的:

在FFPE临床样本中评估6-aza-2-thiothymine (ATT) 作为脂质MALDI-MSI的矩阵
将ATT的性能与已建立的矩阵 (DHB,NOR) 进行脂质分析.
根据脂质概况,评估ATT在区分正常和癌症组织方面的有用性.

主要方法:

在脂质标准上对ATT,DHB和NOR进行比较分析.
在FFPE脑部部分使用ATT在正离子和负离子模式中的脂质的MALDI-MSI分析.
在FFPE质母细胞瘤组织微阵列 (TMA) 上应用ATT以进行本质病理相关性.

主要成果:

在FFPE脑部部分,ATT能够对98种脂质进行假定注释,并平衡地检测出糖脂和脂.
与DHB相比,ATT在识别糖脂和脂肪酸方面表现优于DHB和NOR,并且显示出更高的脂类多样性.
在FFPE样本中,ATT成功地发现了能够区分质母细胞瘤与正常大脑组织的脂质特征.

结论:

即使在高侧分辨率 (20 μm) 中,ATT也是 lipidomic MALDI-MSI 适用于病理学的矩阵.
通过从同一组织部分分析脂质和质,ATT的使用为多组学研究提供了战略优势.
支持积极和负电离模式的脂质组分析,增强其在FFPE组织分析中的多功能性.

关键词:

6-aza-2-thiothymine 的使用情况在FFPE 马尔迪-MSI 空间脂管学

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