Comment[ArrayExpressAccession]	E-GEOD-74385
MAGE-TAB Version	1.1				
Public Release Date	2016-02-15
Investigation Title	Transcriptomic analysis of aggressive meningiomas identifies PTTG1 and LEPR1 as prognostic biomarkers independent of WHO grade				
Comment[Submitted Name]	Transcriptomic analysis of aggressive meningiomas identifies PTTG1 and LEPR1 as prognostic biomarkers independent of WHO grade
Experiment Description	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 af rmed 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. Comparative transcriptomic analysis of 62 low- and high-grade meningiomas				
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl			
Person Last Name	Herold-Mende	Mock	Schmidt	Herold-Mende	
Person First Name	Christel	Andreas	Melissa	Christel	
Person Email	geo@ncbi.nlm.nih.gov				
Person Affiliation	Heidelberg University Hospital				
Person Address	Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, Heidelberg, Germany				
Person Roles	submitter				
Protocol Name	P-GSE74385-1	P-GSE74385-3	P-GSE74385-4	P-GSE74385-2	P-GSE74385-5
Protocol Description	Raw-intensity data were obtained after image analysis of the fluorescent spot intensity reads. All preprocessing and normalization steps were performed in the R programming environment [www.r-project.org]. Inter-array normalization was conducted using qspline normalization in the affy package. Probe sets belonging to one gene were median summarized leading to a reduced number of probes in the normalized data set. Next, a linear model was fitted to account for different batches (limma package). Lastly, intra-array normalization was performed by means of median-centering data and followed by log2 transformation. ID_REF =  VALUE = qspline normalized, median-centered log2 values Detection Pval = 	Standard labeling protocol of Genomic Core Facility of the German Cancer Research Center (DKFZ, Heidelberg, Germany)	Standard Illumina hybridization protocol	Total RNA was extracted from tissue using the AllPrep Kit (Qiagen) according to manufacturer's instructions. RNA integrity was assessed by the Agilent 2100 Bioanalyzer.	Standard Illumina scanning protocol
Protocol Type	normalization data transformation protocol	labelling protocol	hybridization protocol	nucleic acid extraction protocol	array scanning protocol
Experimental Factor Name	subtype	batch			
Experimental Factor Type	subtype	batch			
Comment[SecondaryAccession]	GSE74385				
Comment[GEOReleaseDate]	2016-02-15				
Comment[ArrayExpressSubmissionDate]	2015-10-27				
Comment[GEOLastUpdateDate]	2016-02-16				
Comment[AEExperimentType]	transcription profiling by array				
Comment[AdditionalFile:Data1]	GSE74385_non-normalized.txt				
Comment[AdditionalFile:Data2]	GSE74385_normalized.txt				
SDRF File	E-GEOD-74385.sdrf.txt