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| Status |
Public on Dec 31, 2011 |
| Title |
Expression of Epithelial-to-Mesenchymal Transition (EMT)-associated genes in extratumoral microenvironment predicts poor clinical outcome in breast cancer patients |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Introduction: A gene expression signature indicative of active wound responses is common to more than 90% of non-neoplastic tissues adjacent to breast cancer, but these tissues also show substantial heterogeneity, suggesting different microenvironmental subtypes. Genomic variation in the extratumoral microenvironment has received limited study.
Methods: Gene expression analysis from 72 patient-derived samples adjacent to invasive breast cancer or ductal carcinoma in situ was evaluated. Unsupervised clustering identified two distinct gene expression subgroups that differed substantially in expression of genes associated with epithelial-to-mesenchymal transition (EMT). We evaluated the prognostic and biological relevance of this extratumoral EMT-like signature using clinical and experimental approaches.
Results: We found that the extratumoral EMT-like signature was not significantly associated with overall survival among all patients [Hazard Ratio (HR) = 1.4, 95% CI 0.6 - 2.8, p=0.337], but there was a strong association with overall survival among estrogen receptor (ER)-positive patients [HR = 2.5, 95% CI 0.9 – 6.7, p=0.062] or hormone-treated patients [HR=2.6, 95% CI 1.0 – 7.0, p=0.045]. In addition, co-culturing of ER-positive MCF-7 cells with cells undergoing EMT increased migration of MCF7 cells in a TGF-β1 dependent manner.
Conclusion: Together, these results suggest that the presence of an EMT-like signature in the cancer-adjacent extratumoral microenvironment may influence the aggressiveness of the ER-positive tumors and that ER-positive patients with these extratumoral signatures may require additional treatments or more aggressive surgeries.
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| Overall design |
Reference vs. test sample. 74 test samples (12 breast tumors, 62 normal tissue adjacent to breast tumor) from 72 patients.
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| |
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| Contributor(s) |
Román-Pérez E, Troester MA |
| Citation(s) |
22429463 |
| Submission date |
Aug 22, 2011 |
| Last update date |
Feb 22, 2018 |
| Contact name |
Melissa Troester |
| E-mail(s) |
troester@unc.edu
|
| Organization name |
University of North Carolina at Chapel Hill
|
| Department |
Epidemiology
|
| Street address |
135 Dauer Drive, CB 7435
|
| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599 |
| Country |
USA |
| |
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| Platforms (5)
|
| GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
| GPL8264 |
UNC PerouLab 244K Custom Human Array version 3 |
| GPL8269 |
UNC PerouLab 244K Custom Human Array version 5 |
| GPL8274 |
UNC PerouLab 244K Custom Human Array version 3 with barcode-15847 |
| GPL10481 |
Agilent-scanner-UNC-custom-4X44K-without-Virus |
|
| Samples (74)
|
|
| Relations |
| BioProject |
PRJNA145607 |
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