Article
Gene expression of mitotic drivers TPX2 and RAN is upregulated dependent on meningioma grade and correlates with MIB-1 labeling index
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Authors
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Sergej Telentschak
- Allgemeine Neurochirurgie, Uniklinik Köln, Klinikum der Universität zu Köln, Zentrum für Neurochirurgie, Labor für Neuroonkologie und experimentelle Neurochirurgie, Köln, Deutschland
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Gabriele Röhn
- Allgemeine Neurochirurgie, Uniklinik Köln, Köln, Deutschland
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Lukas Görtz
- Allgemeine Neurochirurgie, Uniklinik Köln, Köln, Deutschland
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Niklas von Spreckelsen
- Klinikum der Universität zu Köln, Zentrum für Neurochirurgie, Klinik für Allgemeine Neurochirurgie, Köln, Deutschland
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Pantelis Stavrinou
- Neurochirurgische Abteilung, Uniklinik Köln, Uniklinik Köln, Köln, Deutschland
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Roland Goldbrunner
- Klinikum der Universität zu Köln, Zentrum für Neurochirurgie, Klinik für Allgemeine Neurochirurgie, Köln, Deutschland
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Marco Timmer
- Allgemeine Neurochirurgie, Uniklinik Köln, Klinikum der Universität zu Köln, Zentrum für Neurochirurgie, Klinik für Allgemeine Neurochirurgie, Köln, Deutschland
| Published: | June 9, 2017 |
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Outline
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Objective: There is still no effective chemotherapy regimen for malignant meningiomas. Numerous studies on different malignancies indicate that Ran (Ras-related nuclear protein), some components of its pathway and TPX2 (Targeting protein for Xenopus kinesin-like protein 2) are involved in tumorigenesis, cancer progression and tumor cell survival. Mitotic spindle formation is regulated Ran-dependently by TPX2. Due to its Ran-regulated transportation into the nucleus, TPX2 promotes DNA damage response. To evaluate a potential role of TPX2 and Ran pathway in meningiomas we measured their gene expression in different tumor types.
Methods: Using quantitative RT-PCR, gene expression was analyzed in 77 meningiomas including WHO I° (n=27), II° (n=31), III° (n=19) and 10 brain tissues as control. MIB-1 labeling indices were obtained from histopathology reports. Results were depicted by mean values (±SEM) in Arbitrary Units. Statistical analysis was performed using Mann-Whitney U test, Kruskal Wallis test with post hoc analysis, Spearman's correlation and Receiver Operator Characteristics (ROC) analysis. A value of P<0.05 was considered significant.
Results: Significant TPX2 gene overexpression compared to control (0.42±0.12) was detected in all meningioma WHO grades (I°: 0.91±0.15; II°: 1.93±0.28; III°: 4.33±0.67). With increasing WHO grade there was a steady increase of TPX2 (P<0.01). RAN was significantly overexpressed in WHO III° (2.42±0.29) versus control (1.45±0.12) and showed a significant rise from WHO I° to III° and from II° to III°. Spearman's correlation of RAN and TPX2 was moderate in first diagnosed tumors (r=0.518, P=0.003). In ROC analysis, TPX2 showed predictive properties as biomarker differentiating WHO I° from II°, II° from III° and I° from III° with the areas under the curve of 0.725, 0.791 and 0.912, respectively (each P<0.01). MIB-1 labeling index correlated highly with TPX2 (r=0.865) and moderately with RAN (r=0.619) as well as with Ran pathway components RAN-BP1 (r=0.639) and RCC1 (r=0.675).
Conclusion: TPX2 and RAN were significantly overexpressed in malignant meningioma and correlated with MIB-1. This could implicate them as potential driving force for malignant transformation. Therefore, TPX2 and components of Ran pathway may represent future markers for diagnosis and prognosis as well as targets for chemotherapy in malignant meningioma.
