Laboratory of Molecular Neuro-Oncology, Departments of Neurosurgery, Hematology and Medical Oncology, School of Medicine, and Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
Neuro Oncol. 2011 Sep;13(9):926-42. doi: 10.1093/neuonc/nor078.
Gliomas are a group of aggressive brain tumors that diffusely infiltrate adjacent brain tissues, rendering them largely incurable, even with multiple treatment modalities and agents. Mostly asymptomatic at early stages, they present in several subtypes with astrocytic or oligodendrocytic features and invariably progress to malignant forms. Gliomas are difficult to classify precisely because of interobserver variability during histopathologic grading. Identifying biological signatures of each glioma subtype through protein biomarker profiling of tumor or tumor-proximal fluids is therefore of high priority. Such profiling not only may provide clues regarding tumor classification but may identify clinical biomarkers and pathologic targets for the development of personalized treatments. In the past decade, differential proteomic profiling techniques have utilized tumor, cerebrospinal fluid, and plasma from glioma patients to identify the first candidate diagnostic, prognostic, predictive, and therapeutic response markers, highlighting the potential for glioma biomarker discovery. The number of markers identified, however, has been limited, their reproducibility between studies is unclear, and none have been validated for clinical use. Recent technological advancements in methodologies for high-throughput profiling, which provide easy access, rapid screening, low sample consumption, and accurate protein identification, are anticipated to accelerate brain tumor biomarker discovery. Reliable tools for biomarker verification forecast translation of the biomarkers into clinical diagnostics in the foreseeable future. Herein we update the reader on the recent trends and directions in glioma proteomics, including key findings and established and emerging technologies for analysis, together with challenges we are still facing in identifying and verifying potential glioma biomarkers.
神经胶质瘤是一组侵袭性脑肿瘤,它们广泛浸润邻近的脑组织,使得它们即使采用多种治疗方式和药物也难以治愈。在早期阶段,它们大多没有症状,表现为星形细胞瘤或少突胶质细胞瘤的多种亚型,并且不可避免地会发展为恶性形式。由于在组织病理学分级过程中存在观察者间的变异性,因此神经胶质瘤很难进行精确分类。因此,通过对肿瘤或肿瘤邻近液体的蛋白质生物标志物进行分析,确定每个神经胶质瘤亚型的生物学特征具有非常重要的意义。这种分析不仅可以为肿瘤分类提供线索,还可以确定临床生物标志物和病理靶点,从而开发个性化治疗方法。在过去的十年中,差异蛋白质组学分析技术利用神经胶质瘤患者的肿瘤、脑脊液和血浆来鉴定第一批候选诊断、预后、预测和治疗反应标志物,突出了神经胶质瘤生物标志物发现的潜力。然而,所鉴定的标志物数量有限,其在研究之间的可重复性尚不清楚,并且没有一种标志物被验证可用于临床应用。最近在高通量分析方法方面的技术进步,为快速筛选、低样本消耗和准确的蛋白质鉴定提供了便利,预计将加速脑肿瘤生物标志物的发现。可靠的生物标志物验证工具有望在可预见的未来将生物标志物转化为临床诊断。本文将为读者更新神经胶质瘤蛋白质组学的最新趋势和方向,包括关键发现以及现有的和新兴的分析技术,以及在确定和验证潜在的神经胶质瘤生物标志物方面我们仍然面临的挑战。