Metabolic profiles of human brain parenchyma and glioma for rapid tissue diagnosis by targeted desorption electrospray ionization mass spectrometry.

Metabolic profiles of human brain parenchyma and glioma for rapid tissue diagnosis by targeted desorption electrospray ionization mass spectrometry.
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DOI:
10.1007/s00216-021-03593-0
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发表时间:
2021-10
影响因子:
4.3
通讯作者:
Cooks RG
Cooks RG
中科院分区:
化学2区
文献类型:
--
作者:
Chen R;Brown HM;Cooks RG

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解吸电喷雾离子化质谱法(DES-MS)非常适合于术中组织分析,因为它需要很少的样品制备并且提供快速和灵敏的分子诊断。目前,胶质瘤活检的肿瘤细胞百分比的术中评估可以通过测量单个代谢物N-乙酰天冬氨酸(NAA)来进行。包括额外的生物标志物可能会提高准确性时,区分脑实质胶质瘤的CDMA-MS。为了探索这种可能性,质谱记录提取物从32个未经修改的人脑样本与已知的病理。对从全扫描和多反应监测(MRM)曲线获得的数据进行统计分析,鉴定了鉴别代谢物,即γ-氨基丁酸(GABA)、肌酸、谷氨酸、肉毒碱、己烷-1,2,3,4,5,6-己醇(缩写为hexol)以及已确立的生物标志物NAA。脑实质很容易区分胶质瘤的基础上,这些代谢产物的测量都在全扫描质谱和其特征MRM转换的强度。新的EST-MS方法(5分钟采集使用全扫描和MS/MS),开发测量这些代谢物之间的离子丰度比,进行了测试,使用29个大脑样本的涂片。基于GABA、肌酸、肉毒碱和己醇信号的离子丰度比均具有> 90%的灵敏度、> 80%的特异性和> 85%的准确性。因此,诊断离子丰度比的实施应加强个体生物标志物的区分能力,并增强方法对信号波动的鲁棒性,从而导致神经胶质瘤诊断的改进的HPLC-MS方法。
Desorption electrospray ionization mass spectrometry (DESI-MS) is well suited for intraoperative tissue analysis since it requires little sample preparation and offers rapid and sensitive molecular diagnostics. Currently, intraoperative assessment of the tumor cell percentage of glioma biopsies can be made by measuring a single metabolite, N-acetylaspartate (NAA). The inclusion of additional biomarkers will likely improve the accuracy when distinguishing brain parenchyma from glioma by DESI-MS. To explore this possibility, mass spectra were recorded for extracts from 32 unmodified human brain samples with known pathology. Statistical analysis of data obtained from full scan and multiple reaction monitoring (MRM) profiles identified discriminatory metabolites, namely gamma-aminobutyric acid (GABA), creatine, glutamic acid, carnitine, hexane-1,2,3,4,5,6-hexol (abbreviated as hexol), as well as the established biomarker NAA. Brain parenchyma was readily differentiated from glioma based on these metabolites as measured both in full scan mass spectra and by the intensities of their characteristic MRM transitions. New DESI-MS methods (5 min acquisition using full scans and MS/MS), developed to measure ion abundance ratios among these metabolites, were tested using smears of 29 brain samples. Ion abundance ratios based on signals for GABA, creatine, carnitine and hexol all had sensitivities >90%, specificities >80%, and accuracies >85%. Prospectively, the implementation of diagnostic ion abundance ratios should strengthen the discriminatory power of individual biomarkers and enhance method robustness against signal fluctuations, resulting in an improved DESI-MS method of glioma diagnosis.
DOI: 10.1111/neup.12671
发表时间: 2020-12-01
期刊: NEUROPATHOLOGY
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影响因子: 2
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DOI: 10.3389/fonc.2018.00462
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