Artikel
Impairments of intracellular signaling observed in patients with diffuse gliomas
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Autoren
Veröffentlicht: | 18. Juni 2018 |
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Gliederung
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Objective: Abnormal signaling through the pores of the nuclear as well as the cell membrane has been recently documented in patients with diffuse gliomas (DG). However, it remains to be elucidatedwhether the impairments of signaling at both subcellular localizations underly the same pathomechanism. Our work was directed to study for the first time specific parameters-indexes of both the nucleocytoplasmic and intra-extracellular transport in patients with DG.
Methods: We analysed semiquantitatively via immunohistochemistry the nuclear expressions of HIF-1A and KPNA2 as well as the cytoplasmic of Kv10.1, VEGF-R2 and KPNA2 in 93 patients with DG (23 WHO grade II, 23 WHO grade III and 47 WHO grade IV, GBMs). Clinical data have been retrieved retrospectively. Mean follow up was estimated at 35 months. Statistic analysis using standard methods (chi-square, rho, t-test, Kaplan-Meier method, Cox regression analysis) was performed via SPSS 24.
Results: Patients with GBM were more likely to express lower values of Kv.10.1(p<0.001) as well as higher of KPNA2 (p<0.001). A trend for an inverse correlation between expressions ofKv.10.1and KPNA2 has been detected (p=0.08). Lower expressions of Kv.10.1and KPNA2 have been identified as beneficial prognostic factors of OS and PFS in patients with WHO grade III (cytoplasmic Kv.10.1<1%, OS: p=0.03, PFS: p=0.01) and IV (nuclear KPNA2<10%, OS: p=0.03, PFS: p=0.05), respectively.
Conclusion: Our study identified Kv.10.1as a novel diagnostic and prognostic biomarker in patients with DG. Furthermore, we observed a trend for an inverse correlation of KPNA2 and Kv.10.1 providing indices for a common pathomechanism involved in the impairments of both intra-extracellular and nucleocytoplasmic signaling observed in patients with DG.