In situ biomarker discovery and label-free molecular histopathological diagnosis of lung cancer by ambient mass spectrometry imaging.
In situ biomarker discovery and label-free molecular histopathological diagnosis of lung cancer by ambient mass spectrometry imaging.
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DOI：
10.1038/srep14089
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发表时间：
2015-09-25
影响因子：
4.6
通讯作者：
Abliz Z
中科院分区：
文献类型：
--
作者：
Li T;He J;Mao X;Bi Y;Luo Z;Guo C;Tang F;Xu X;Wang X;Wang M;Chen J;Abliz Z
在代谢组水平上对肿瘤新陈代谢的敏感和空间探索是极具挑战性的。在这项研究中，我们发展了一种基于空气流动辅助解吸电喷雾电离(AFADESI)的环境质量成像的原位代谢组学方法，可以高灵敏度地在空间上探索组织中整体代谢物的变化。使用这种方法，我们从52例肺癌术后组织样本中发现了潜在的组织病理学诊断生物标记物(包括脂类、氨基酸、胆碱、多肽和肉碱)，并随后使用这些生物标记物生成图像，用于快速且无标记的组织病理学诊断。这些生物标志物的敏感度和特异度分别为93.5%和100%。此外，对冷冻切片进行的一次成像分析花费了数十分钟，显示了所有这些生物标志物，揭示了癌症的类型和亚型。该方法有可能成为临床肺癌快速诊断和即时影像引导手术的分子病理学工具。
Sensitive and spatial exploration of the metabolism of tumors at the metabolome level is highly challenging. In this study, we developed an in situ metabolomics method based on ambient mass spectrometry imaging using air flow-assisted desorption electrospray ionization (AFADESI), which can spatially explore the alteration of global metabolites in tissues with high sensitivity. Using this method, we discovered potential histopathological diagnosis biomarkers (including lipids, amino acids, choline, peptides, and carnitine) from 52 postoperative lung cancer tissue samples and then subsequently used these biomarkers to generate images for rapid and label-free histopathological diagnosis. These biomarkers were validated with a sensitivity and a specificity of 93.5% and 100%, respectively. Moreover, a single imaging analysis of a cryosection that visualized all these biomarkers, taking tens of minutes, revealed the type and subtype of the cancer. This method could potentially be used as a molecular pathological tool for rapid clinical lung cancer diagnosis and immediate image-guided surgery.