Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue.
Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue.
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DOI：
10.1007/s00216-016-9627-4
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发表时间：
2016-08
影响因子：
4.3
通讯作者：
Cooks RG
中科院分区：
文献类型：
--
作者：
Alfaro CM;Jarmusch AK;Pirro V;Kerian KS;Masterson TA;Cheng L;Cooks RG
接触喷雾质谱法（TS-MS）是一种环境电离技术（在露天电离未处理的样品），可用于术中快速识别癌组织的疾病状态和确定手术切缘。在该研究中，在来自21名患有肾细胞癌（RCC）的人类受试者的新鲜肾组织（约1- 5cm 3）上在切除后1小时内进行TS-MS。TS-MS数据取自新鲜切除的组织的初步诊断价值进行了评价。负离子模式（m/z 700-1000）数据的主成分分析（PCA）提供了RCC（16个样品）和健康肾组织（13个样品）之间的分离。基于组织病理学评价，对PCA压缩数据的线性判别分析（LDA）估计灵敏度（真阳性率）和特异性（真阴性率）分别为98%和95%。结果表明，TS-MS可能提供快速诊断信息，尽管未经处理的肾脏组织的复杂性和存在的干扰，如尿液和血液。在TS-MS分析后对组织标本进行负离子模式下的解吸电喷雾电离成像（ESI-MSI）作为参考方法。DESI成像实验提供了磷脂谱（m/z 700-1000），其也在PCA空间中分离RCC和健康组织，PCA-LDA灵敏度和特异性分别为100%和89%。TS和DESI上样图表明，不同离子对RCC与健康肾组织的分离贡献最大（TS的m/z 794 [PC 34：1+Cl]−和844 [PC 38：4+Cl]−，DESI的m/z 788 [PS 36：1-H]−和810 [PS 38：4-H]−），而m/z 885（[PI 38：4-H]−）在TS和DESI中均很重要。的前景，剩余的障碍，和未来的工作需要翻译TS-MS到术中组织诊断的方法进行了讨论。
Touch spray - mass spectrometry (TS-MS) is an ambient ionization technique (ionization of unprocessed samples in the open air) that may find intraoperative applications in quickly identifying the disease state of cancerous tissues and in defining surgical margins. In this study, TS-MS was performed on fresh kidney tissue (~1–5 cm3), within one hour of resection, from 21 human subjects afflicted by renal cell carcinoma (RCC). The preliminary diagnostic value of TS-MS data taken from freshly resected tissue was evaluated. Principal component analysis (PCA) of the negative ion mode (m/z 700–1000) data provided separation between RCC (16 samples) and healthy renal tissue (13 samples). Linear discriminant analysis (LDA) on the PCA compressed data estimated sensitivity (true positive rate) and specificity (true negative rate) of 98% and 95%, respectively, based on histopathological evaluation. The results indicate that TS-MS might provide rapid diagnostic information in spite of the complexity of unprocessed kidney tissue and the presence of interferences such as urine and blood. Desorption electrospray ionization imaging (DESI-MSI) in the negative ionization mode was performed on the tissue specimens after TS-MS analysis as a reference method. The DESI imaging experiments provided phospholipid profiles (m/z 700–1000) that also separated RCC and healthy tissue in the PCA space, with PCA-LDA sensitivity and specificity of 100% and 89%, respectively. The TS and DESI loading plots indicated that different ions contributed most to the separation of RCC from healthy renal tissue (m/z 794 [PC 34:1+Cl]− and 844 [PC 38:4+Cl]− for TS vs. m/z 788 [PS 36:1-H]− and 810 [PS 38:4-H]− for DESI), while m/z 885 ([PI 38:4-H]−) was important in both TS and DESI. The prospect, remaining hurdles, and future work required for translating TS-MS into a method of intraoperative tissue diagnosis is discussed.