Transcriptomics

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Relationship of mammographic density and gene expression: analysis of normal breast tissue surrounding breast cancer


ABSTRACT: Purpose: Previous studies of breast tissue gene expression have demonstrated that the extratumoral microenvironment has substantial variability across individuals, some of which can be attributed to epidemiologic factors. To evaluate how mammographic density (MD) and breast tissue composition relate to extratumoral microenvironment gene expression, we used data on 121 breast cancer patients from the population-based Polish Women’s Breast Cancer Study.Design: Breast cancer cases were classified based on a previously reported, biologically-defined extratumoral gene expression signature with two subtypes: an Active subtype, which is associated with high expression of genes related to fibrosis and wound response, and an Inactive subtype, which has high expression of cellular adhesion genes. MD of the contralateral breast was assessed using pre-treatment mammograms and a quantitative, reliable computer-assisted thresholding method. Breast tissue composition was evaluated based on digital image analysis of tissue sections. Results:The Inactive extratumoral subtype was associated with significantly higher percentage mammographic density (PD) and dense area (DA) in univariate analysis (PD: p=0.001; DA: p=0.049) and in multivariable analyses adjusted for age and body mass index (PD: p=0.004; DA: p=0.049). Inactive/higher MD tissue was characterized by a significantly higher percentage of stroma and a significantly lower percentage of adipose tissue, with no significant change in epithelial content. Analysis of published gene expression signatures suggested that Inactive/higher MD tissue expressed increased estrogen response and decreased TGF-ß signaling. Conclusions:By linking novel molecular phenotypes with MD, our results indicate that MD reflects broad transcriptional changes, including changes in both epithelia- and stroma-derived signaling. reference x sample

ORGANISM(S): Homo sapiens  

SUBMITTER: Aleix Prat  Melissa Troester   Melissa A Troester   Xuezheng Sun    

PROVIDER: E-GEOD-49175 | ArrayExpress | 2013-10-21

SECONDARY ACCESSION(S): GSE49175PRJNA215168

REPOSITORIES: GEO, ArrayExpress

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Relationship of mammographic density and gene expression: analysis of normal breast tissue surrounding breast cancer.

Sun Xuezheng X   Gierach Gretchen L GL   Sandhu Rupninder R   Williams Tyisha T   Midkiff Bentley R BR   Lissowska Jolanta J   Wesolowska Ewa E   Boyd Norman F NF   Johnson Nicole B NB   Figueroa Jonine D JD   Sherman Mark E ME   Troester Melissa A MA  

Clinical cancer research : an official journal of the American Association for Cancer Research 20130805 18


PURPOSE:Previous studies of breast tissue gene expression have shown that the extratumoral microenvironment has substantial variability across individuals, some of which can be attributed to epidemiologic factors. To evaluate how mammographic density and breast tissue composition relate to extratumoral microenvironment gene expression, we used data on 121 patients with breast cancer from the population-based Polish Women's Breast Cancer Study. EXPERIMENTAL DESIGN:Breast cancer cases were classif  ...[more]

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