Schmidt, Melissa and Mock, Andreas and Jungk, Christine and Sahm, Felix and Ull, Anna Theresa and Warta, Rolf and Lamszus, Katrin and Gousias, Konstantinos and Ketter, Ralf and Roesch, Saskia and Rapp, Carmen and Schefzyk, Sebastian and Urbschat, Steffi and Lahrmann, Bernd and Kessler, Almuth F. and Loehr, Mario and Senft, Christian and Grabe, Niels and Reuss, David and Beckhove, Philipp and Westphal, Manfred and von Deimling, Andreas and Unterberg, Andreas and Simon, Matthias and Herold-Mende, Christel (2016) Transcriptomic analysis of aggressive meningiomas identifies PTTG1 and LEPR as prognostic biomarkers independent of WHO grade. ONCOTARGET, 7 (12). pp. 14551-14568. ISSN 1949-2553,
Full text not available from this repository. (Request a copy)Abstract
Meningiomas are frequent central nervous system tumors. Although most meningiomas are benign (WHO grade I) and curable by surgery, WHO grade II and III tumors remain therapeutically challenging due to frequent recurrence. Interestingly, relapse also occurs in some WHO grade I meningiomas. Hence, we investigated the transcriptional features defining aggressive (recurrent, malignantly progressing or WHO grade III) meningiomas in 144 cases. Meningiomas were categorized into non-recurrent (NR), recurrent (R), and tumors undergoing malignant progression (M) in addition to their WHO grade. Unsupervised transcriptomic analysis in 62 meningiomas revealed transcriptional profiles lining up according to WHO grade and clinical subgroup. Notably aggressive subgroups (R+M tumors and WHO grade III) shared a large set of differentially expressed genes (n = 332; p < 0.01, FC > 1.25). In an independent multicenter validation set (n = 82), differential expression of 10 genes between WHO grades was confirmed. Additionally, among WHO grade I tumors differential expression between NR and aggressive R+M tumors was affirmed for PTTG1, AURKB, ECT2, UBE2C and PRC1, while MN1 and LEPR discriminated between NR and R+M WHO grade II tumors. Univariate survival analysis revealed a significant association with progression-free survival for PTTG1, LEPR, MN1, ECT2, PRC1, COX10, UBE2C expression, while multivariate analysis identified a prediction for PTTG1 and LEPR mRNA expression independent of gender, WHO grade and extent of resection. Finally, stainings of PTTG1 and LEPR confirmed malignancy-associated protein expression changes. In conclusion, based on the so far largest study sample of WHO grade III and recurrent meningiomas we report a comprehensive transcriptional landscape and two prognostic markers.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-TRANSFORMING GENE; ACUTE MYELOID-LEUKEMIA; POOR-PROGNOSIS; ANAPLASTIC MENINGIOMAS; INCREASED EXPRESSION; KINASE INHIBITOR; GLIOMA PATIENTS; PHASE-I; MATRIX METALLOPROTEINASE-2; INTRACRANIAL MENINGIOMAS; meningioma; anaplastic; recurrent; transcriptomic analysis; biomarker |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Apr 2019 11:16 |
| Last Modified: | 03 Apr 2019 11:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3229 |
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