title: High-mobility group AT-hook protein 2 expression and its prognostic significance in MGMT methylated and unmethylated glioblastoma.
abstract: High-mobility group AT-hook protein 2 (HMGA 2) is a transcription factor associated with malignancy and poor prognosis in a variety of human cancers. We correlated HMGA 2 expression with clinical parameters, survival, and O-6-methylguanine-DNA methyltransferase methylation status (MGMT) in glioblastoma patients. HMGA 2 expression was determined by performing quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in 44 glioblastoma patients and 5 non-tumorous brain specimens as controls. Gene expression levels of MGMT methylated vs. unmethylated patients, and gene expression levels between patient groups, both for qPCR and IHC data were compared using the Mann-Whitney U test. The relationship between HMGA 2 expression, progression-free survival and overall survival was analyzed using the Kaplan-Meier method and the log-rank test. P-values of <0.05 were considered statistically significant throughout the analyses. The mean age of patients at diagnosis was 57.4 ± 15.7 years, and the 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 levels (IRS mean, 17.21; SD, 7.43 vs. 3.20; SD, 1.68) (p=0.001). Survival analysis revealed that HMGA 2 overexpression was associated with a shorter progression-free and overall survival time in patients with methylation (n=24). The present study shows a tendency that HMGA 2 overexpression correlates with a poor prognosis of glioblastoma patients independent of MGMT methylation status. The results suggest that HMGA 2 could play an important role in the treatment of glioblastoma and could have a function in prognosis of this type of cancer.
authors.affiliation: Department of Neurosurgery, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Schwarm
authors.affiliation: Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Uhle
authors.affiliation: Institute of Neuropathology, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Schänzer
authors.affiliation: Institute of Neuropathology, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Acker
authors.affiliation: Department of Neurosurgery, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Stein
authors.affiliation: Department of Neurosurgery, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Marcus H T
authors.initials: MH
authors.lastname: Reinges
authors.affiliation: Department of Neurosurgery, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weischer
authors.affiliation: Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Weigand
authors.affiliation: Department of Neurosurgery, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Uhl
authors.affiliation: Department of Neurosurgery, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Malgorzata A
authors.initials: MA
authors.lastname: Kolodziej
mesh_terms: D000328:Adult; D000368:Aged; D019175:DNA Methylation / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D025743:HMGA2 Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D025743:HMGA2 Protein; D019853:O(6)-Methylguanine-DNA Methyltransferase