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Series GSE45275 Query DataSets for GSE45275
Status Public on Mar 15, 2016
Title Digital expression profiling identifies CDC5L, RECQL4, and CDK4 as potential oncogenes in a cohort of pediatric osteosarcoma tumours
Organism Homo sapiens
Experiment type Other
Summary Osteosarcoma is the most common malignancy of bone, and occurs most frequently in children and adolescents. Currently, the most reliable technique for prognostication is measuring histopathologic tumor necrosis following preoperative chemotherapy, and favourable prognosis is signified by 90% or greater estimated necrosis of the tumour. Neither genetic testing nor molecular biomarkers have been described for this tumour. We used the novel nanoString mRNA expression analysis system to analyzed total RNA from 35 flash-frozen sporadic paediatric osteosarcoma biopsy and resection specimens to quantify mRNA expression for 17 oncogenes and tumour suppressor genes. Three oncogenes, cell cycle regulator gene CDC5L, the RecQ DNA helicase gene RECQL4, and the cyclin-dependent kinase gene CDK4, were more highly expressed (p<0.05) in tumours which responded poorly to neoadjuvant chemotherapy. A similar trend (p<0.10) was identified for the osteoblast-specific transcription factor gene RUNX2. No statistically significant difference existed in comparing expression of CDC5L, RECQL4, CDK4, and RUNX2 between biopsy and resection samples. Additionally, analysis of expression data in the context of histological subtype yielded preliminary results for deducing molecular subtypes of osteosarcomas. Osteoblastic osteosarcomas possessed higher expression of CDKN1A, PTEN, and RUNX2 relative to their fibroblastic counterparts (p<0.05). This research study shows that CDC5L, RECQL4, and CDK4 tumour expression levels may be useful for identifying patients who may not benefit from the current standardized chemotherapy regimen.
Overall design Total RNA was isolated from 52 pediatric osteosarcoma samples (prechemotherapy biopsies and resections), 3 osteosarcoma cell lines, and normal human osteoblasts. nanoString mRNA expression analysis was applied to samples split between 3 batches to compare samples based on clinical and pathologic data reports, and to compare samples with normal human osteoblasts. For 43 samples, there were complete data and the RNA was successfully assayed. Analysis was performed using R.
Contributor(s) Martin JW, Chilton-MacNeill S, Squire JA, Zielenska M
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Submission date Mar 19, 2013
Last update date Mar 15, 2016
Contact name Jeff W Martin
Organization name Hospital for Sick Children
Street address 555 University Avenue
City Toronto
State/province ON
ZIP/Postal code M5G 1X8
Country Canada
Platforms (1)
GPL16814 Zielenska Lab custom nanoString nCounter gene expression codeset
Samples (144)
GSM1100546 A_rep1
GSM1100547 A_rep2
GSM1100548 A_rep3
BioProject PRJNA193395

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE45275_RCCCollectorDataAnalysisGuidelines.pdf.gz 1.4 Mb (ftp)(http) PDF
GSE45275_raw_signals.txt.gz 8.7 Kb (ftp)(http) TXT
Processed data included within Sample table

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