From the Department of Pathology; Department of Neuropathology, St. Mary's Hospita, Kurume, Japan.
Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
J Neuropathol Exp Neurol. 2020 Aug 1;79(8):873-879. doi: 10.1093/jnen/nlaa058.
Leucine-rich α-2 glycoprotein 1 (LRG1) is a diagnostic marker candidate for glioblastoma. Although LRG1 has been associated with angiogenesis, it has been suggested that its biomarker role differs depending on the type of tumor. In this study, a clinicopathological examination of LRG1's role as a biomarker for glioblastoma was performed. We used tumor tissues of 155 cases with diffuse gliomas (27 astrocytomas, 14 oligodendrogliomas, 114 glioblastomas). The immunohistochemical LRG1 intensity scoring was classified into 2 groups: low expression and high expression. Mutations of IDH1, IDH2, and TERT promoter were analyzed through the Sanger method. We examined the relationship between LRG1 expression level in glioblastoma and clinical parameters, such as age, preoperative Karnofsky performance status, tumor location, extent of resection, O6-methylguanine DNA methyltransferase promoter, and prognosis. LRG1 high expression rate was 41.2% in glioblastoma, 3.7% in astrocytoma, and 21.4% in oligodendroglioma. Glioblastoma showed a significantly higher LRG1 expression than lower-grade glioma (p = 0.0003). High expression of LRG1 was an independent favorable prognostic factor (p = 0.019) in IDH-wildtype glioblastoma and correlated with gross total resection (p = 0.002) and the tumor location on nonsubventricular zone (p = 0.00007). LRG1 demonstrated multiple potential as a diagnostic, prognostic, and regional biomarker for glioblastoma.
富含亮氨酸α-2 糖蛋白 1（LRG1）是胶质母细胞瘤的候选诊断标志物。尽管 LRG1 与血管生成有关，但有人认为其作为生物标志物的作用因肿瘤类型而异。在这项研究中，对 LRG1 作为胶质母细胞瘤生物标志物的作用进行了临床病理检查。我们使用了 155 例弥漫性神经胶质瘤（27 例星形细胞瘤、14 例少突胶质细胞瘤、114 例胶质母细胞瘤）的肿瘤组织。通过免疫组化对 LRG1 强度评分进行分类：低表达和高表达。通过 Sanger 法分析 IDH1、IDH2 和 TERT 启动子的突变。我们研究了 LRG1 在胶质母细胞瘤中的表达水平与临床参数（如年龄、术前卡诺夫斯基表现状态、肿瘤位置、切除范围、O6-甲基鸟嘌呤 DNA 甲基转移酶启动子和预后）之间的关系。胶质母细胞瘤的 LRG1 高表达率为 41.2%，星形细胞瘤为 3.7%，少突胶质细胞瘤为 21.4%。胶质母细胞瘤的 LRG1 表达明显高于低级别神经胶质瘤（p=0.0003）。在 IDH 野生型胶质母细胞瘤中，LRG1 的高表达是独立的有利预后因素（p=0.019），与大体全切除（p=0.002）和非脑室区肿瘤位置（p=0.00007）相关。LRG1 显示出作为胶质母细胞瘤的诊断、预后和区域性生物标志物的多种潜力。
