Abstract A105: Identification of gene expression profiles associated with different types of breast adipose and their relationship to tumorigenesis

Abstract

Abstract Background: Research over the past decade has shown the importance of the stroma in tumorigenesis, however, having long been thought to function only as an inert energy storage depot, the role of adipose tissue in tumor etiology has been largely ignored. Improved understanding of the role of adipose in tumor development and progression is crucial given the increasing rates of obesity and the use of autologous fat transfer in breast reconstruction. Methods: Adipose, adjacent to and distant from invasive breast tumors, was laser microdissected from 20 post-menopausal women, and from 20 post-menopausal women with non-malignant breast disease. Gene expression data were generated using U133 2.0 microarrays. After quality control and visualization steps, the data were analyzed to identify significant patterns of differential expression between adipose classes, at the individual gene and molecular pathway level. A subset of genes were further analyzed by qRT-PCR in out-of-sample adipose specimens. Results: Pathway analysis revealed significant differences in immune response between non-malignant, distant and tumor adjacent adipose. 141 genes were differentially expressed (FDR <0.05, >2-fold difference) between tumor-adjacent and non-malignant breasts including FCGR2A, FOLR2, LGMN and NLRP3. These four genes were also differentially expressed (FDR <0.05, >2-fold difference) between distant and non-malignant adipose. Within invasive breasts, no genes were differentially expressed using FDR <0.05, however, RRM2, PLA2G7, MMP9, MMP12, CHI3L1, SPP1 were expressed at >3-fold higher levels (P<0.05) in tumor-adjacent compared to distant adipose. Conclusions: Gene expression levels differ in breast adipose, depending on presence of or proximity to tumor cells. Tumor-adjacent and distant adipose from invasive breasts both exhibit increased expression in genes involved in the M2 anti-inflammatory response, suggesting that the microenvironment in an invasive breast has a decreased immune response compared to the non-malignant microenvironment. Genes expressed at higher levels in tumor-adjacent compared to distant adipose are associated with increased cellular proliferation, invasion, migration, angiogenesis and metastasis, suggesting that tumor-adjacent adipose promotes the growth and progression of the tumor. Together, these data suggest that adipose is not an inert component of the breast microenvironment but plays an active role in tumorigenesis. Citation Format: Lori Field, Brenda Deyarmin, Ryan van Laar, Craig Shriver, Rachel Ellsworth. Identification of gene expression profiles associated with different types of breast adipose and their relationship to tumorigenesis. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A105.