Transcriptomic analysis of aggressive meningiomas identifies PTTG1 and LEPR as prognostic biomarkers independent of WHO grade
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Transcriptomic analysis of aggressive meningiomas identifies PTTG1 and LEPR as prognostic biomarkers independent of WHO grade. / Schmidt, Melissa; Mock, Andreas; Jungk, Christine; Sahm, Felix; Ull, Anna Theresa; Warta, Rolf; Lamszus, Katrin; Gousias, Konstantinos; Ketter, Ralf; Roesch, Saskia; Rapp, Carmen; Schefzyk, Sebastian; Urbschat, Steffi; Lahrmann, Bernd; Kessler, Almuth F; Löhr, Mario; Senft, Christian; Grabe, Niels; Reuss, David; Beckhove, Philipp; Westphal, Manfred; von Deimling, Andreas; Unterberg, Andreas; Simon, Matthias; Herold-Mende, Christel.
in: ONCOTARGET, Jahrgang 7, Nr. 12, 22.03.2016, S. 14551-68.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Transcriptomic analysis of aggressive meningiomas identifies PTTG1 and LEPR as prognostic biomarkers independent of WHO grade
AU - Schmidt, Melissa
AU - Mock, Andreas
AU - Jungk, Christine
AU - Sahm, Felix
AU - Ull, Anna Theresa
AU - Warta, Rolf
AU - Lamszus, Katrin
AU - Gousias, Konstantinos
AU - Ketter, Ralf
AU - Roesch, Saskia
AU - Rapp, Carmen
AU - Schefzyk, Sebastian
AU - Urbschat, Steffi
AU - Lahrmann, Bernd
AU - Kessler, Almuth F
AU - Löhr, Mario
AU - Senft, Christian
AU - Grabe, Niels
AU - Reuss, David
AU - Beckhove, Philipp
AU - Westphal, Manfred
AU - von Deimling, Andreas
AU - Unterberg, Andreas
AU - Simon, Matthias
AU - Herold-Mende, Christel
PY - 2016/3/22
Y1 - 2016/3/22
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.18632/oncotarget.7396
DO - 10.18632/oncotarget.7396
M3 - SCORING: Journal article
C2 - 26894859
VL - 7
SP - 14551
EP - 14568
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 12
ER -
