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

Author:

Tsidulko Alexandra Y1,Kazanskaya Galina M12,Kostromskaya Diana V2,Aidagulova Svetlana V3,Kiselev Roman S23,Volkov Alexandr M2,Kobozev Vyacheslav V2,Gaitan Alexei S4,Krivoshapkin Alexei L234,Grigorieva Elvira V1

Affiliation:

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

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

3. Novosibirsk State Medical University, Novosibirsk, Russia

4. European Medical Center, Moscow, Russia

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.

Publisher

IOS Press

Subject

General Medicine

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