NG2/CSPG4、CD44和Ki-67在胶质母细胞瘤患者中的预后相关性

Prognostic relevance of NG2/CSPG4, CD44 and Ki-67 in patients with glioblastoma.

作者信息

Tsidulko Alexandra Y, Kazanskaya Galina M, Kostromskaya Diana V, Aidagulova Svetlana V, Kiselev Roman S, Volkov Alexandr M, Kobozev Vyacheslav V, Gaitan Alexei S, Krivoshapkin Alexei L, Grigorieva Elvira V

机构信息

1 Institute of Molecular Biology and Biophysics, Novosibirsk, Russia.

2 Meshalkin Research Institute of Circulation Pathology, Novosibirsk, Russia.

出版信息

Tumour Biol. 2017 Sep;39(9):1010428317724282. doi: 10.1177/1010428317724282.

DOI:10.1177/1010428317724282

PMID:28945172

Abstract

Neuron-glial antigen 2 (NG2, also known as CSPG4) and hyaluronic acid receptor CD44 are chondroitin sulphate proteoglycans actively involved in brain development and its malignant transformation. Here, we aimed to compare prognostic significances of NG2, CD44 and Ki-67 expression in glioblastoma multiforme patients. Totally, 45 tissue samples and 83 paraffin-embedded tissues for 75 patients were analysed. The prognostic values of the genes were analysed using Kaplan-Meier survival curves. Grade III gliomas showed 2-fold difference in NG2 expression between anaplastic astrocytoma and oligoastrocytoma (10.1 ± 3.5 and 25.5 ± 14.5, respectively). For grade IV gliomas, upregulated NG2 expression (21.0 ± 6.8) was associated with poor glioblastoma multiforme prognosis (overall survival < 12 months) compared with glioblastoma multiforme patients with good prognosis (4.4 ± 3.2; overall survival > 12 months). Multivariate survival analysis using Cox proportional hazards model confirmed that high NG2 expression was associated with low survival of the patients (hazard ratio: 3.43; 95% confidence interval: 1.18-9.93; p = 0.02), whereas age (hazard ratio: 1.02; 95% confidence interval: 0.96-1.09; p = 0.42), tumour resection (hazard ratio: 1.03; 95% confidence interval: 0.98-1.08; p = 0.25) and sex (hazard ratio: 0.62; 95% confidence interval: 0.21-1.86; p = 0.40) did not show significant association with prognosis. Although the positive correlation was shown for NG2 and CD44 expression in the glioblastomas (Pearson coefficient = 0.954), Kaplan-Meier and multivariate survival analyses did not revealed a significant association of the increased CD44 expression (hazard ratio: 2.18; 95% confidence interval: 0.50-9.43; p = 0.30) or high Ki-67 proliferation index (hazard ratio: 1.10; 95% confidence interval: 1.02-1.20; p = 0.02) with the disease prognosis. The results suggest that upregulation of NG2/CSPG4 rather than changes in CD44 or Ki-67 expression is associated with low overall survival in glioblastoma multiforme patients, supporting NG2/CSPG4 as a potential prognostic marker in glioblastoma.

摘要

神经元胶质抗原2（NG2，也称为CSPG4）和透明质酸受体CD44是硫酸软骨素蛋白聚糖，积极参与脑发育及其恶性转化。在此，我们旨在比较多形性胶质母细胞瘤患者中NG2、CD44和Ki-67表达的预后意义。总共分析了75例患者的45个组织样本和83个石蜡包埋组织。使用Kaplan-Meier生存曲线分析基因的预后价值。III级胶质瘤显示间变性星形细胞瘤和少突星形细胞瘤之间NG2表达有2倍差异（分别为10.1±3.5和25.5±14.5）。对于IV级胶质瘤，与预后良好的多形性胶质母细胞瘤患者（4.4±3.2；总生存期>12个月）相比，NG2表达上调（21.0±6.8）与多形性胶质母细胞瘤预后不良（总生存期<12个月）相关。使用Cox比例风险模型进行的多变量生存分析证实，高NG2表达与患者低生存率相关（风险比：3.43；95%置信区间：1.18-9.93；p=0.02），而年龄（风险比：1.02；95%置信区间：0.96-1.09；p=0.42）、肿瘤切除（风险比：1.03；95%置信区间：0.98-1.08；p=0.25）和性别（风险比：0.62；95%置信区间：0.21-1.86；p=0.40）与预后无显著关联。尽管在胶质母细胞瘤中NG2和CD44表达呈正相关（Pearson系数=0.954），但Kaplan-Meier和多变量生存分析未显示CD44表达增加（风险比：2.18；95%置信区间：0.50-9.43；p=0.30）或高Ki-67增殖指数（风险比：1.10；95%置信区间：1.02-1.20；p=0.02）与疾病预后有显著关联。结果表明，多形性胶质母细胞瘤患者中NG2/CSPG4上调而非CD44或Ki-67表达变化与低总生存期相关，支持NG2/CSPG4作为胶质母细胞瘤的潜在预后标志物。