Department of Chemistry, Purdue University, West Lafayette, IN, USA.
Department of Neurological Surgery, Indiana University School of Medicine, Goodman Campbell Brain and Spine, Indianapolis, IN, USA.
J Appl Lab Med. 2021 Jul 7;6(4):902-916. doi: 10.1093/jalm/jfaa233.
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.
手术肿瘤切除是弥漫性神经胶质瘤（最常见的恶性脑癌）的主要治疗选择。术中使用分子诊断可提高对肿瘤核心样本中神经胶质瘤的诊断。此外，手术切缘处的残留肿瘤是肿瘤复发和恶性进展的主要原因。本研究评估了一种解吸电喷雾电离质谱（DESI-MS）系统，用于术中异柠檬酸脱氢酶（IDH）突变评估、肿瘤细胞浸润估计（肿瘤细胞百分比，TCP）和疾病状态。这些信息可用于增强安全切除范围，从而可能改善患者预后。
对移动 DESI-MS 仪器进行了修改，并在 49 名接受开颅手术切除疑似弥漫性神经胶质瘤的患者的神经外科手术室（OR）中使用。通过 DESI-MS 在 OR 中分析来自肿瘤核心和手术切缘的小组织活检（ntotal = 203），并使用单变量和多变量统计方法进行分类。
使用 DESI-MS/MS 测量肿瘤核心中 2-羟基戊二酸（2-HG）离子强度评估 IDH 突变状态，得到敏感性、特异性和总体诊断准确性分别为 89%、100%和 94%（ncore = 71）。使用 N-乙酰天冬氨酸（NAA）强度评估肿瘤边缘和核心活检中的 TCP（分类为低或高），得到敏感性、特异性和准确性分别为 91%、76%和 83%（ntotal = 203）。使用脂质谱解卷积评估 TCP，得到敏感性、特异性和准确性分别为 76%、85%和 81%（ntotal = 203）。结合实验数据和 PCA-LDA 对疾病状态的预测，预测疾病状态的敏感性、特异性和准确性分别为 63%、83%和 74%（ntotal = 203）。
DESI-MS 系统允许在大型人类神经胶质瘤队列中识别 IDH 突变状态、诊断神经胶质瘤和术中估计肿瘤细胞浸润。该方法应进一步完善，以用于临床诊断应用。
