Transcriptomics

Dataset Information

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Ovarian Cancer Dataset


ABSTRACT: 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. 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.

ORGANISM(S): Homo sapiens  

SUBMITTER: Johnathan Lancaster   Douglas Marchion  Steven Eschrich 

PROVIDER: E-GEOD-23554 | ArrayExpress | 2011-10-02

SECONDARY ACCESSION(S): GSE23554PRJNA133365

REPOSITORIES: GEO, ArrayExpress

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Publications


Despite initial sensitivity to chemotherapy, ovarian cancers (OVCA) often develop drug resistance, which limits patient survival. Using specimens and/or genomic data from 289 patients and a panel of cancer cell lines, we explored genome-wide expression changes that underlie the evolution of OVCA chemoresistance and characterized the BCL2 antagonist of cell death (BAD) apoptosis pathway as a determinant of chemosensitivity and patient survival.Serial OVCA cell cisplatin treatments were performed  ...[more]

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