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E-GEOD-7849 - Transcription profiling of human breast tumors to identify age-specific differences of oncogenic pathway deregulation

Status
Submitted on 18 May 2007, released on 15 June 2008, last updated on 27 March 2012
Organism
Homo sapiens
Samples (78)
Array (1)
Protocols (2)
Description
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 Experiment Overall Design: n=78
Experiment types
transcription profiling by array, unknown experiment type
Contact
Citation
Age-specific differences in oncogenic pathway deregulation seen in human breast tumors. Carey K Anders, Chaitanya R Acharya, David S Hsu, Gloria Broadwater, Katherine Garman, John A Foekens, Yi Zhang, Yixin Wang, Kelly Marcom, Jeffrey R Marks, Sayan Mukherjee, Joseph R Nevins, Kimberly L Blackwell, Anil Potti. PLoS ONE 3(1):e1373 (2008)
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-7849.idf.txt
Sample and data relationshipE-GEOD-7849.sdrf.txt
Processed data (1)E-GEOD-7849.processed.1.zip
Array designA-AFFY-1.adf.txt
Links