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Series GSE23554 Query DataSets for GSE23554
Status Public on Oct 03, 2011
Title Ovarian Cancer Dataset
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Background. Genome-wide expression changes are associated with development of chemoresistance in patients with ovarian cancer (OVCA); the BCL2 antagonist of cell death (BAD) apoptosis pathway may play a role in clinical outcome.
Methods. We analyzed specimens and/or genomic data from 1,406 patients and 116 cancer cell lines. Genome-wide expression changes and cisplatin-resistance were evaluated in OVCA cell lines subjected to a total of 144 (cisplatin)-treatment/recovery cycles. Pathway analysis was performed on genes associated with increasing cisplatin-resistance. BAD protein phosphorylation was studied in patient samples and cell lines, and small interfering RNAs (siRNA) used to explore the pathway as a therapeutic target. We evaluated the influence of BAD-pathway expression on chemosensitivity and/or clinical outcome using genomic data from 60 human cancer cell lines and ovarian, breast, colon, and brain cancers from 1,258 patients.
Results. The BAD pathway was associated with evolution of OVCA cell line cisplatin-resistance (P<0.001) and resistance of 7 human cancer cell types to 8 cytotoxic agents (P<0.05). OVCA chemoresistance was associated with BAD protein phosphorylation, and targeted siRNA modulation produced corresponding changes in chemosensitivity. Expression of a 47-gene BAD-pathway signature was associated with survival of 1,258 patients with ovarian, breast, colon, and brain cancer. The OVCA BAD-pathway signature survival advantage was independent of surgical cytoreductive status.
Conclusions. The BAD apoptosis pathway influences the sensitivity of human cancers to a variety of chemotherapies, likely via modulation of BAD-phosphorylation. The pathway has clinical relevance as a potential biomarker of therapeutic response, patient survival, and as a promising therapeutic target.
 
Overall design Twenty-eight (28) advanced-stage serous epithelial ovarian cancers were resected at the time of primary surgery from patients who would receive platinum-based therapy. The tumors were arrayed on Affymetrix HG-U133A GeneChips. The samples were analyzed with respect to the BAD pathway for correlation to overall survival and cisplatin response.
 
Contributor(s) Marchion D, Lancaster J, Eschrich S
Citation(s) 21849418
Submission date Aug 10, 2010
Last update date Aug 10, 2018
Contact name Steven Eschrich
E-mail Steven.Eschrich@moffitt.org
Organization name Moffitt Cancer Center
Department Biostatistics & Bioinformatics
Street address 12902 Magnolia Drive
City Tampa
State/province FL
ZIP/Postal code 33612
Country USA
 
Platforms (1)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
Samples (28)
GSM577823 Ovarian Cancer - Sample D1462
GSM577824 Ovarian Cancer - Sample D1858
GSM577825 Ovarian Cancer - Sample D2147
This SubSeries is part of SuperSeries:
GSE23603 Gene expression in ovarian cancer
Relations
BioProject PRJNA133365

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
GSE23554_RAW.tar 92.8 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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