■高级别神经胶质瘤和颅外起源的脑肿瘤的分化对于决定后续治疗方案至关重要。在高级别神经胶质瘤中,肿瘤块的手术切除是当前标准方案的基本组成部分,在脑转移中,必须考虑原发肿瘤的负担。然而,没有癌症史,在成像中的分化仍然具有挑战性。因此,活检是常见的,可能有助于确定肿瘤的起源。支持差异化的附加工具可能会有很大帮助。为此,我们的目的是基于对小样本组织的表达分析,确定一个生物标志物组,以支持手术切除标本的病理分析.鉴于异常的谷氨酸信号被确定为驱动胶质母细胞瘤的进展,我们专注于谷氨酸受体和谷氨酸稳态的关键参与者。
■根据55例脑肿瘤的手术切除样本,通过RT-PCR分析了离子型和代谢型谷氨酸受体的表达以及谷氨酸稳态的关键参与者。随后,我们进行了受试者工作特征(ROC)分析,以鉴定表达水平可能与胶质母细胞瘤或脑转移相关的基因.
■在分析的总共29个谷氨酸能基因中,9个基因在高级别胶质瘤和脑转移瘤之间呈现显著不同的表达水平。其中,7个被鉴定为潜在的生物标志物候选物,包括编码AMPA受体GRIA1,GRIA2,红藻氨酸受体GRIK1和GRIK4,代谢型受体GRM3,转氨酶BCAT1和谷氨酰胺合成酶(由GLUL编码)的基因.总的来说,生物标志物组预测肿瘤实体的准确率为88%(95%CI:87.1,90.8).基因表达数据,然而,无法区分有癫痫发作的患者和没有癫痫发作的患者。
■我们已经鉴定了一组7个基因,其表达可以作为生物标志物组,在分子水平上区分成胶质细胞瘤和脑转移。经过进一步验证,我们的生物标志物标记在诊断后的后续治疗方案决策中可能非常有用.
UNASSIGNED: The differentiation of high-grade glioma and brain tumors of an extracranial origin is eminent for the decision on subsequent treatment regimens. While in high-grade glioma, a surgical resection of the tumor mass is a fundamental part of current standard regimens, in brain metastasis, the burden of the primary tumor must be considered. However, without a cancer history, the differentiation remains challenging in the imaging. Hence, biopsies are common that may help to identify the tumor origin. An additional tool to support the differentiation may be of great help. For this purpose, we aimed to identify a biomarker panel based on the expression analysis of a small sample of tissue to support the pathological analysis of surgery resection specimens. Given that an aberrant glutamate signaling was identified to drive glioblastoma progression, we focused on glutamate receptors and key players of glutamate homeostasis.
UNASSIGNED: Based on surgically resected samples from 55 brain tumors, the expression of ionotropic and metabotropic glutamate receptors and key players of glutamate homeostasis were analyzed by RT-PCR. Subsequently, a receiver operating characteristic (ROC) analysis was performed to identify genes whose expression levels may be associated with either glioblastoma or brain metastasis.
UNASSIGNED: Out of a total of 29 glutamatergic genes analyzed, nine genes presented a significantly different expression level between high-grade gliomas and brain metastases. Of those, seven were identified as potential biomarker candidates including genes encoding for AMPA receptors GRIA1, GRIA2, kainate receptors GRIK1 and GRIK4, metabotropic receptor GRM3, transaminase BCAT1 and the glutamine synthetase (encoded by GLUL). Overall, the biomarker panel achieved an accuracy of 88% (95% CI: 87.1, 90.8) in predicting the tumor entity. Gene expression data, however, could not discriminate between patients with seizures from those without.
UNASSIGNED: We have identified a panel of seven genes whose expression may serve as a biomarker panel to discriminate glioblastomas and brain metastases at the molecular level. After further validation, our biomarker signatures could be of great use in the decision making on subsequent treatment regimens after diagnosis.