Artikel
Influence of novel AQP1 promoter haplotypes on AQP1 expression, tumor edema as well as two-years survival in patients suffering from glioblastoma multiforme
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Veröffentlicht: | 4. Juni 2012 |
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Objective: Water channel proteins (AQP) are overexpressed in brain tumors, mediating cell proliferation and angiogenesis. We investigated the influence of two AQP1 promoter single nucleotide polymorphisms (-783C > G)/(-781C > T) defining novel AQP1 haplotypes on gene expression and their influence on peritumoral edema as well as two-years survival of patients suffering from glioblastoma multiforme.
Methods: Reporter activity, transcription factor binding and gene expression, dependent on (-783C > G)/(-781C > T) haplotypes was conducted in HELA cells and blood tissue. After genotyping of 151 patients suffering from GBM, comparison to healthy control and evaluation with respect to tumor edema as well as two-years survival was performed. Immunhistochemical staining of GBM tissue sections was conducted to depict AQP1 expression.
Results: Two single nucleotide polymorphisms (-783C > G/-781C > T) define 6 common haplotypes with altered reporter activity, allele specific transcription factor binding and AQP1 gene expression. The haplotype distribution in GBM is comparable to healthy control. At the two-years follow-up 122 (80.8%) of the 151 patients had died. Kaplan-Meier curves revealed significant differences in two-years survival according to the different haplotypes (p = 0.04), while there was no difference in peritumoral edema. Immunhistochemical staining revealed strong AQP1 expression on all GBM sections independent to the haplotype.
Conclusions: AQP1 promoter haplotypes might be predictive markers for survival of patients suffering from glioblastoma multiforme.