Artikel
High-mobility group AT-hook protein 2 (HMGA 2) expression in MGMT methylated and unmethylated glioblastoma
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Veröffentlicht: | 8. Juni 2016 |
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Gliederung
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Objective: HMGA 2 is a transcription factor associated with malignancy and poor prognosis in a variety of human cancers. In this study we investigated the HMGA 2 expression in methylated and unmethylated human glioblastomas and its prognostic value with regard to survival time of patients.
Method: In 44 glioblastoma patients and 5 non-tumorous brain specimens as controls HMGA 2 expression was determined by performing quantitative real-time PCR (qPCR) and immunohistochemistry (IHC). Gene expression levels in MGMT methylated vs. unmethylated glioblatoma cells and between tumors and normal brain tissue, were compared using the Mann-Whitney U test. The relationship between HMGA 2 expression, progression-free-, and overall survival was analyzed using the Kaplan-Meier method and the log-rank test. P-values of <0.05 were considered as statistically significant.
Results: Patients' mean age at diagnosis was 57.4 ± 15.7 years. Median survival was 16 months (SE 2.8, 95% CI: 10.6-21.4). HMGA 2 gene expression was significantly higher in glioblastoma compared to normal brain tissue on qPCR (mean: 0.35, SD: 0.27 vs. 0.03, SD: 0.05) and IHC level (IRS mean: 17.21, SD: 7.43 vs. 3.20, SD:1.68) (p=0.001). Survival analysis in methylated patients (n=24) showed that high HMGA 2 levels are associated with a shorter median progression free survival compared to patients with low HMGA 2 expression (10.0 versus 21.0 months; p=0.14). Median overall survival time in patients with HMGA 2 overexpression was 20 months compared to 28 months in HMGA 2 low expression group (p=0.38). Unmethylated (n=18) patients with HMGA 2 overexpression showed no significant differences to the methylated group.
Conclusions: HMGA2 overexpression seems to be associated with a poor prognosis in glioblastoma patients. This protein may be an informative biomarker and prognostic factor independent of the MGMT promoter methylation status.