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Series GSE7849 Query DataSets for GSE7849
Status Public on Jan 16, 2008
Title Age-Specific Differences of Oncogenic Pathway Deregulation Seen in Human Breast Tumors
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Breast cancer arising in young women has a poorer prognosis, is less likely to be hormone sensitive, and represents a particularly challenging clinical entity. The biology driving the aggressive nature of breast cancer arising in young women has yet to be defined.
Among 784 patients with early stage breast cancer, using prospectively-defined, age-specific cohorts (young <= 45 years; older >= 65 years), 411 eligible patients (n = 200 < 45 years; n = 211 >= 65 years) with clinically-annotated Affymetrix microarray data were identified. Gene set enrichment analyses, signatures of oncogenic pathway deregulation and predictors of chemotherapy sensitivity were evaluated within the two age-defined cohorts.
In comparing deregulation of oncogenic pathways between age groups, a statistically higher probability of PI3K (p = 0.006) and Myc (p = 0.03) pathway deregulation was observed in the tumors of younger women. When evaluating unique patterns of pathway deregulation, a low probability of Src and E2F deregulation in tumors of younger women, concurrent with activation of PI3K, Myc, and beta-catenin, conferred a worse prognosis (HR = 4.15; p = 0.008). In contrast, a higher probability of Src and E2F pathway activation in tumors of older women, concurrent low probability of PI3K, Myc and beta-catenin deregulation, was associated with a poorer outcome (HR = 2.7; p = 0.006). Similar pathway differences were identified using gene set enrichment analysis. Importantly, in multivariate analyses including clinico-pathologic variables, genomic clusters of pathway deregulation were identified to be independent predictors of disease-free survival. Finally, a significant relationship (p = 0.02) between anthracycline sensitivity and genomic clusters was observed among women aged >= 65 years.

Submitters do not have approval to publish the .CEL files
Keywords: Retrospective analyses
 
Overall design n=78
 
Contributor(s) Anders CK, Acharya CR, Hsu DS, Broadwater G, Garman K, Foekens JA, Zhang Y, Wang Y, Marcom PK, Marks JR, Mukherjee S, Nevins JR, Blackwell KL, Potti A
Citation(s) 18167534
Submission date May 18, 2007
Last update date Dec 13, 2018
Contact name Carey K. Anders
E-mail(s) ander118@mc.duke.edu
Phone 919-970-6149
Fax 919-684-3309
Organization name Duke University
Department Institute for Genome Sciences and Policy
Lab Potti Lab
Street address 101 Science Drive
City Durham
State/province NC
ZIP/Postal code 27710
Country USA
 
Platforms (1)
GPL8300 [HG_U95Av2] Affymetrix Human Genome U95 Version 2 Array
Samples (78)
GSM190415 DU1: Breast tumors from women with early stage breast cancer
GSM190416 DU2: Breast tumors from women with early stage breast cancer
GSM190417 DU3: Breast tumors from women with early stage breast cancer
Relations
BioProject PRJNA99983

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Supplementary data files not provided
Processed data included within Sample table
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