부산대학교 도서관

BACKGROUND:: Despite a dismal prognosis, variability exists regarding the survival-time in patients with glioblastoma-multiforme (GBM), which may be explained by genetic variation. A possible candidate-gene for such variation is Aquaporin-1 (AQP1), since Aquaporin-1-expression influences the pathogenesis and outcome of various malignancies. Functional genetic variants in the promoter of AQP1, modifying Aquaporin-1-expression, could be associated with altered survival in patients with GBM. METHODS:: We sequenced the human AQP1-promoter to detect novel sequence variants, which might impact on Aquaporin-1-expression and tested the hypothesis, that functional single nucleotide polymorphisms are associated with different survival-times of patients suffering from GBM. RESULTS:: Sequencing the AQP1-promoter revealed a novel −783G/C-polymorphism. Reporter-assays showed that substitution of G for C was associated both with increased transcriptional-activation of the AQP 1-promoter by serum and with increased AQP1 mRNA expression. Finally, we assessed in a cohort of 155 Caucasian patients with GBM whether the functional single-nucleotide-783G/C-polymorphism is associated with survival-time. Cox-regression analyses revealed the AQP1 −783G/C genotype status as an independent prognostic-factor when jointly considering other predictors of survival. Homozygous CC subjects had a significantly worse outcome compared to GC/GG genotypes (hazard ratio: 3.09; 95% CI, 1.43–6.65; P = 0.004). CONCLUSIONS:: Our findings suggest the novel AQP1 polymorphism as a survival prognosticator in patients suffering from GBM that could help to identify a subgroup of patients at high risk for death. Further studies are necessary to reveal the exact molecular mechanisms. J. Surg. Oncol. 2013; 108:492–498. © 2013 Wiley Periodicals, Inc.