NDRG2 and NDRG4 Expression Is Altered in Glioblastoma and Influences Survival in Patients with MGMT-methylated Tumors.

Autor: Kolodziej MA; Department of Neurosurgery, Justus Liebig University, Giessen, Germany malgorzata.kolodziej@neuro.med.uni-giessen.de., Weischer C; Department of Neurosurgery, Justus Liebig University, Giessen, Germany., Reinges MH; Department of Neurosurgery, Justus Liebig University, Giessen, Germany., Uhl E; Department of Neurosurgery, Justus Liebig University, Giessen, Germany., Weigand MA; Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany., Schwarm FP; Department of Neurosurgery, Justus Liebig University, Giessen, Germany., Schänzer A; Department of Neuropathology, Justus Liebig University, Giessen, Germany., Acker T; Department of Neuropathology, Justus Liebig University, Giessen, Germany., Quint K; Department of Neuropathology, Erlangen University Hospital, Erlangen, Germany., Uhle F; Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany., Stein M; Department of Neurosurgery, Justus Liebig University, Giessen, Germany.
Jazyk: angličtina
Zdroj: Anticancer research [Anticancer Res] 2016 Mar; Vol. 36 (3), pp. 887-97.
Abstrakt: Aim: The N-myc down-regulated gene (NDRG) family is a group of genes that have predominantly tumor-suppressive effects. The goal of this study was to investigate the expression of NDRG2 and NDRG4 in surgical specimens of human glioblastoma and in normal brain tissue, and to search for correlations with overall (OS) and progression-free survival (PFS).
Materials and Methods: Samples from 44 patients (31 males, 13 females; mean age±SD=57.4±15.7 years) with primary (n=40) or recurrent glioblastoma (n=4) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry, with dimensionless semiquantitative immunoreactivity score (IRS), ranging from 0-30] for expression of NDRG2 and NDRG4. Five non-tumorous autopsy brain specimens were used as controls.
Results: On the protein level, expression of NDRG2 was significantly down-regulated in glioblastoma (IRS=3.5±3.0 vs. 8.8±3.3; p=0.001), while expression of NDRG4 was significantly up-regulated (IRS=5.4±3.7 vs. 0.75±0.4 vs, p<0.001). There was no statistically significant difference in PFS between a group of 15 patients with glioblastoma with MGMT methylation and enhanced expression of NDRG4 mRNA who were treated with adjuvant radiochemotherapy (temozolomide and 60 Gy) and a group of patients with low expression of NDRG4 mRNA [10 (range=5.5-14.2) months vs. 21 (range=10.7-31.3) months] (p=0.13).
Conclusion: Expression of both NDRG2 and NDRG4 genes is significantly altered in glioblastomas. PFS among the patients with glioblastoma with MGMT methylation treated with radiochemotherapy differed significantly in high-expression groups compared to patients without MGMT methlation and without radiochemotherapy (p<0.05).
(Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
Databáze: MEDLINE