Transcriptomics

Dataset Information

8

Normal breast tissue of obese women is enriched for macrophage markers and macrophage-associated gene expression


ABSTRACT: Activation of inflammatory pathways is one plausible mechanism underlying the association between obesity and increased breast cancer risk. However, macrophage infiltration and local biomarkers of inflammation in breast adipose tissue have seldom been studied in association with obesity. Gene expression profiles of normal breast tissue from reduction mammoplasty patients were evaluated by whole genome microarrays to identify patterns associated with obesity status (normal-weight, body mass index (BMI) <25; overweight, BMI 25-29.9; obese, BMI > or equal to 30). The presence of macrophage-enriched inflammatory loci with immunopositivity for CD68 protein was evaluated by immunohistochemistry (IHC). After adjusting for confounding by age, 760 genes were differentially expressed (203 up and 557 down; FDR = 0.026) between normal-weight and obese women. Gene ontology analysis suggested significant enrichment for pathways involving IL-6, IL-8, CCR5 signaling in macrophages and RXRalpha and PPARalpha activation, consistent with a pro-inflammatory state and suggestive of macrophage infiltration. Gene set enrichment analysis also demonstrated that the genomic signatures of monocytes and macrophages were over-represented in the obese group with FDR of 0.08 and 0.13, respectively. Increased macrophage infiltration was confirmed by IHC, which showed that the breast adipose tissue of obese women had higher average macrophage counts (mean = 8.96 vs. 3.56 in normal-weight women) and inflammatory foci counts (mean = 4.91 vs. 2.67 in normal-weight women). Obesity is associated with local inflammation and macrophage infiltration in normal human breast adipose tissues. Given the role of macrophages in carcinogenesis, these findings have important implications for breast cancer etiology and progression. 72 normal breast tissue samples from patients undergoing reduction mammoplasty. Reference design.

ORGANISM(S): Homo sapiens  

SUBMITTER: Carol Bigelow   D J Jerry  Patricia Casbas-Hernandez  Sallie S Schneider  Melissa Troester  Melissa A Troester  Xuezheng Sun  Liza Makowski 

PROVIDER: E-GEOD-33526 | ArrayExpress | 2011-11-08

SECONDARY ACCESSION(S): GSE33526PRJNA148793

REPOSITORIES: GEO, ArrayExpress

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Normal breast tissue of obese women is enriched for macrophage markers and macrophage-associated gene expression.

Sun Xuezheng X   Casbas-Hernandez Patricia P   Bigelow Carol C   Makowski Liza L   Joseph Jerry D D   Smith Schneider Sallie S   Troester Melissa A MA  

Breast cancer research and treatment 20111015 3


Activation of inflammatory pathways is one plausible mechanism underlying the association between obesity and increased breast cancer risk. However, macrophage infiltration and local biomarkers of inflammation in breast adipose tissue have seldom been studied in association with obesity. Gene expression profiles of normal breast tissue from reduction mammoplasty patients were evaluated by whole genome microarrays to identify patterns associated with obesity status (normal-weight, body mass index  ...[more]

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