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| Status |
Public on Jul 01, 2016 |
| Title |
Age and estrogen-dependent inflammation in breast adenocarcinoma and normal breast tissue [cohort_1] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Chronic inflammation promotes breast tumor growth and invasion by accelerating angiogenesis and tissue remodeling in the tumor microenvironment. The relationship between inflammation and estrogen, which drives the growth of 70 percent of breast tumors, is complex. Low levels of estrogen exposure stimulate macrophages and other inflammatory cell populations, but very high levels are immune suppressive. Breast tumor incidence is increased by obesity and age, which interact to influence inflammatory cell populations in normal breast tissue. The molecular impact of these factors on tumor initiation and growth is not well-understood. We modeled the difference in gene expression between 195 breast adenocarcinomas and 195 matched adjacent normal breast tissue samples, using age, body mass index (BMI), and tumor subtype as covariates. Age and BMI were independently associated with inflammation in normal tissue but not tumors. Older patients with ER-positive disease had tumors with higher levels of Estrogen Receptor (ER) signaling compared to adjacent normal tissue and had lower relative levels of tumor macrophage expression. We developed a novel statistic to quantify the rewiring of gene co-expression networks and demonstrate that in ER-positive tumors basal gene networks are rewired even though their expression levels of these genes are not significantly different from those in adjacent normal tissue. Patient age influences the molecular profile of ER-positive breast tumors. Our data support an immunosuppressive effect of estrogen signaling in the breast tumor microenvironment, suggesting this effect contributes to the greater presence of prognostic and therapeutically relevant immune cells in ER-negative tumors.
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| Overall design |
137 total samples: 43 mammaplastic reduction, 47 breast adenocarcinoma, 47 paired adjacent normal breast tissue
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| Contributor(s) |
Quigley DA, Kristensen V |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Jul 14, 2015 |
| Last update date |
Feb 22, 2018 |
| Contact name |
David Quigley |
| Organization name |
UCSF
|
| Department |
Helen Diller Comprehensive Cancer Center
|
| Lab |
Ashworth Lab
|
| Street address |
1450 Third St. Room 207
|
| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
|
| Samples (137)
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| This SubSeries is part of SuperSeries: |
| GSE70951 |
Paired Breast Adenocarcinoma and Adjacent Normal tissue |
|
| Relations |
| BioProject |
PRJNA289897 |
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