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Series GSE37543 Query DataSets for GSE37543
Status Public on Jun 01, 2013
Title Subtype-specific response to bevacizumab is reflected in the metabolome and transcriptome of breast cancer xenografts
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The VEGF targeted antiangiogenic drug bevacizumab has shown varying results in clinical trials of breast cancer. Identifying robust biomarkers for selecting patients that may benefit from bevacizumab treatment and for monitoring of response is important for the future use of this drug. Two established xenograft models representing basal-like and luminal-like breast cancer were used to study bevacizumab treatment response on the metabolic and gene expression levels. Mice given no treatment or treated with bevacizumab, doxorubicin or the combination of these two drugs were sacrificed at day 3 or 10. High resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) and gene expression microarray analysis was performed on all tumor samples. Combination treatment with bevacizumab had the strongest growth inhibiting effect in the basal-like tumors, and this was reflected in a significant response in the metabolomic and transcriptomic profiles. In the luminal-like xenografts, addition of bevacizumab did not improve the effect of doxorubicin. On the global transcriptomic level, the largest changes in gene expression were observed for the most efficient treatment in each of the two xenograft models. The metabolite glycerophosphocholine (GPC) showed opposite response in the treated xenografts compared with untreated controls: lower in basal-like tumors and higher in luminal-like tumors. Lower levels of creatine, taurine and glycine were observed in the basal-like xenografts given bevacizumab as monotherapy compared with untreated xenografts. Comparing combination therapy with doxorubicin monotherapy in basal-like xenografts, 14 genes showed significant differential expression, including higher expression of very low density lipoprotein receptor (VLDLR), and lower expression of hemoglobin, theta 1 (HBQ1). Using published gene expression signatures, bevacizumab treated tumors were associated with a more hypoxic phenotype, while no evidence was found for associations between bevacizumab treatment and vascular invasion or increasing tumor grade. This study underlines the importance of characterizing biological differences between subtypes of breast cancer to identify personalized biomarkers for selecting patients for bevacizumab treatment and evaluating response to therapy.
 
Overall design 60 samples are analyzed. For each of the two xenograft models, tumors were collected from animals that were untreated or treated with bevacizumab (5 mg/kg), doxorubicin (8 mg/kg) or a combination of the two therapies (n = 6 tumors for each group). Bevacizumab treatment was repeated at day 4 and day 7. Animals were sacrificed and tissue harvested at either day 3 or 10 after treatment, in triplicates within each treatment group. This resulted in 24 tumor samples from each of the models. In addition, untreated and bevacizumab treated luminal-like xenografts not fed with estradiol were included for comparison (n = 12). Note that the untreated controls are overlapping with the samples in the GEO series with accession number: GSE25915.
 
Contributor(s) Borgan E, Lindholm EM, Moestue S, Maelandsmo GM, Lingjaerde OC, Gribbestad IS, Borresen-Dale A, Engebraaten O, Sorlie T
Citation(s) 23142657, 31088535
Submission date Apr 24, 2012
Last update date May 29, 2019
Contact name Eldrid Borgan
E-mail(s) eldrid.borgan@gmail.com
Organization name Oslo University Hospital Radiumhospitalet
Department Genetics
Street address Ullernchausseen 70
City Oslo
ZIP/Postal code 0310
Country Norway
 
Platforms (1)
GPL6480 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version)
Samples (60)
GSM921359 MAS98.06 control day3 mouse No2 Right Side
GSM921360 MAS98.12 doxoribicin day10 mouse No62 Left Side
GSM921361 MAS98.12 bevacizumab-doxorubicin day10 mouse No2 Right Side
Relations
BioProject PRJNA161845

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
GSE37543_RAW.tar 464.8 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table
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