Yamanoi Yu, Fujii Masazumi, Murakami Yuta, Nagai Kenichiro, Hoshi Kyoka, Hashimoto Yasuhiro, Honda Takashi, Saito Kiyoshi, Kitazume Shinobu
Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan.
Department of Biochemistry, Fukushima Medical University, Fukushima, Japan.
Neurooncol Adv. 2020 Apr 30;2(1):vdaa055. doi: 10.1093/noajnl/vdaa055. eCollection 2020 Jan-Dec.
High-grade glioma is the most pervasive and lethal of all brain malignancies. Despite advances in imaging technologies, discriminating between gliomas and other brain diseases such as multiple sclerosis (MS) often requires brain biopsy. Several reports show that protein tyrosine phosphatase receptor Z (PTPRZ) is highly expressed in glioblastoma, and we found that a soluble cleaved form of PTPRZ (sPTPRZ) was present in the cerebrospinal fluid (CSF). The aim of this study was to determine whether the sPTPRZ level in CSF has utility as a diagnostic marker for glioma.
Microarray datasets from normal brain tissue and brain tumors were obtained from the Gene Expression Omnibus. PTPRZ protein expression in clinical specimens was evaluated by immunohistochemistry. Semiquantitative western blotting was used to measure sPTPRZ levels in CSF samples from patients with glioma, schwannoma, MS, or nontumor disorders.
Expression of PTPRZ mRNA and protein was markedly increased in glioblastoma, astrocytoma, oligodendroglioma, and schwannoma tissues compared with control brain tissue. sPTPRZ was present at significantly elevated levels in the CSF of patients with glioma (grades 1-4), but not in patients with schwannoma or MS, compared with the control samples. Receiver operating characteristic curve analysis showed that sPTPRZ in CSF could discriminate between glioma and MS patients (area under the curve 0.9676; < .0001).
sPTPRZ in CSF is a promising diagnostic biomarker for glioma and could reduce the need for a surgical biopsy.
高级别胶质瘤是所有脑恶性肿瘤中最常见且致命的。尽管成像技术有所进步,但区分胶质瘤与其他脑部疾病(如多发性硬化症,MS)通常仍需要进行脑活检。多项报告显示,蛋白酪氨酸磷酸酶受体Z(PTPRZ)在胶质母细胞瘤中高表达,并且我们发现脑脊液(CSF)中存在可溶性裂解形式的PTPRZ(sPTPRZ)。本研究的目的是确定脑脊液中sPTPRZ水平是否可作为胶质瘤的诊断标志物。
从基因表达综合数据库中获取正常脑组织和脑肿瘤的微阵列数据集。通过免疫组织化学评估临床标本中PTPRZ蛋白的表达。采用半定量蛋白质印迹法测量来自胶质瘤、神经鞘瘤、MS或非肿瘤性疾病患者脑脊液样本中的sPTPRZ水平。
与对照脑组织相比,胶质母细胞瘤、星形细胞瘤、少突胶质细胞瘤和神经鞘瘤组织中PTPRZ mRNA和蛋白的表达明显增加。与对照样本相比,胶质瘤患者(1 - 4级)脑脊液中sPTPRZ水平显著升高,而神经鞘瘤或MS患者脑脊液中sPTPRZ水平未升高。受试者工作特征曲线分析表明,脑脊液中的sPTPRZ可区分胶质瘤和MS患者(曲线下面积为0.9676;P <.0001)。
脑脊液中的sPTPRZ是一种有前景的胶质瘤诊断生物标志物,可减少手术活检的需求。