Intraoperative Mass Spectrometry Platform for IDH Mutation Status Prediction, Glioma Diagnosis, and Estimation of Tumor Cell Infiltration.
Intraoperative Mass Spectrometry Platform for IDH Mutation Status Prediction, Glioma Diagnosis, and Estimation of Tumor Cell Infiltration.
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用于IDH突变状态预测、胶质瘤诊断和肿瘤细胞浸润估计的术中质谱平台。
DOI：
10.1093/jalm/jfaa233
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发表时间：
2021-07-07
期刊：
影响因子：
--
通讯作者：
Cooks RG
中科院分区：
文献类型：
--
作者：
Brown HM;Alfaro CM;Pirro V;Dey M;Hattab EM;Cohen-Gadol AA;Cooks RG
手术切除肿瘤是弥漫性胶质瘤的主要治疗选择，弥漫性胶质瘤是最常见的恶性脑癌。利用分子诊断技术可以提高肿瘤核心标本的术中诊断率。此外，手术切缘的残留肿瘤是肿瘤复发和恶性进展的主要原因。本研究评价解吸电喷雾电离质谱仪(DESI-MS)系统用于术中异柠檬酸脱氢酶(IDH)突变评估、以肿瘤细胞百分比(Tcp)评估肿瘤细胞浸润性以及疾病状态。这一信息可以用来提高安全切除的范围，从而潜在地改善患者的预后。对移动式Desi-MS仪器进行了改进，并在神经外科手术室(ORS)对49名因疑似弥漫性胶质瘤而行开颅肿瘤切除术的受试者进行了研究。对来自肿瘤中心和手术切缘的小组织活检标本(n总数=203例)在OR中进行DESI-MS分析，并采用单因素和多因素统计方法进行分类。使用DESI-MS/MS测量肿瘤核心的2-羟基戊二酸(2-HG)离子强度来评估IDH突变状态，其敏感性、特异性和总体诊断准确率分别为89、100和94%(ncore=71)。用N-乙酰-天冬氨酸(NAA)强度评估肿瘤边缘和核心活检的TcP(分为低或高)的敏感性、特异性和准确性分别为91%、76%和83%(nTotal=203)。使用血脂谱去卷积的Tcp评估提供的敏感性、特异性和准确性分别为76%、85%和81%(n总数=203)。结合实验数据和使用PCA-LDA预测疾病状态，预测疾病状态的敏感度、特异度和准确度分别为63%、83%和74%(nTotal=203)。该DESI-MS系统可用于鉴定IDH突变状态、胶质瘤诊断和术中评估大量人脑胶质瘤队列中肿瘤细胞的浸润性。这一方法学应进一步完善，以应用于临床诊断。
Surgical tumor resection is the primary treatment option for diffuse glioma, the most common malignant brain cancer. The intraoperative diagnosis of gliomas from tumor core samples can be improved by use of molecular diagnostics. Further, residual tumor at surgical margins is a primary cause of tumor recurrence and malignant progression. This study evaluates a desorption electrospray ionization mass spectrometry (DESI-MS) system for intraoperative isocitrate dehydrogenase (IDH) mutation assessment, estimation of tumor cell infiltration as tumor cell percentage (TCP), and disease status. This information could be used to enhance the extent of safe resection and so potentially improve patient outcomes. A mobile DESI-MS instrument was modified and used in neurosurgical operating rooms (ORs) on a cohort of 49 human subjects undergoing craniotomy with tumor resection for suspected diffuse glioma. Small tissue biopsies (ntotal = 203) from the tumor core and surgical margins were analyzed by DESI-MS in the OR and classified using univariate and multivariate statistical methods. Assessment of IDH mutation status using DESI-MS/MS to measure 2-hydroxyglutarate (2-HG) ion intensities from tumor cores yielded a sensitivity, specificity, and overall diagnostic accuracy of 89, 100, and 94%, respectively (ncore = 71). Assessment of TCP (categorized as low or high) in tumor margin and core biopsies using N-acetyl-aspartic acid (NAA) intensity provided a sensitivity, specificity, and accuracy of 91, 76, and 83%, respectively (ntotal = 203). TCP assessment using lipid profile deconvolution provided sensitivity, specificity, and accuracy of 76, 85, and 81%, respectively (ntotal = 203). Combining the experimental data and using PCA-LDA predictions of disease status, the sensitivity, specificity, and accuracy in predicting disease status are 63%, 83%, and 74%, respectively (ntotal = 203). The DESI-MS system allowed for identification of IDH mutation status, glioma diagnosis, and estimation of tumor cell infiltration intraoperatively in a large human glioma cohort. This methodology should be further refined for clinical diagnostic applications.
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影响因子：
9.3
作者：
Ifa DR;Eberlin LS
通讯作者：
Eberlin LS
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.1
作者：
Alfaro, Clint M.;Pirro, Valentina;Cohen-Gadol, Aaron A.
通讯作者：
Cohen-Gadol, Aaron A.
影响因子：
3.9
作者：
Kim, Betty Y. S.;Jiang, Wen;McCutcheon, Ian E.
通讯作者：
McCutcheon, Ian E.
在增强胶质母细胞瘤的增强和非增强部分的肿瘤浸润：与组织病理学的相关性。
影响因子：
3.7
作者：
Eidel O;Burth S;Neumann JO;Kieslich PJ;Sahm F;Jungk C;Kickingereder P;Bickelhaupt S;Mundiyanapurath S;Bäumer P;Wick W;Schlemmer HP;Kiening K;Unterberg A;Bendszus M;Radbruch A
通讯作者：
Radbruch A