Abstract
Abstract
Introduction
Adipose tissue - long believed to be no more than an energy storage organ - is metabolically active and consists of a variety of cell types. Adipocytes, fibroblasts and macrophages reside in adipose tissue and may have tumor-promoting properties through the release of cytokines and other growth stimulating molecules. Further, adipose tissue has the capacity of storing pollutants and carcinogens. Breast tumors are embedded in adipose tissue and the direct interface between tumor and adipose tissue in the breast defines a micro-environment potentially fostering tumor initiation and/or progression. The aim of this study was to investigate the transcriptome of adipose tissue from cancer-bearing breasts, localized either close to or distant from the tumor, in addition to comparing it to adipose tissue from tumor-free breasts.
Methods
We collected adipose tissue from n = 33 tumor-bearing breasts (a) close to (< 2cm) and (b) distant from (>5cm) the tumor and from n = 5 tumor-free breasts to investigate gene expression profiles in these three series of tissues. Gene expression was measured from RNA isolated from fresh frozen adipose tissue using Illumina HT12 bead arrays. Quantile normalized expression values were analyzed between (a) and (b) as well as between (a)+(b) and (c) using t-test. Data was filtered by standard variation of 0.95. P-values ≤0.001 were considered significant.
Results
We did not observe any significant differences in gene expression when comparing adipose tissue close to or distant from the tumor. By contrast, expression profiles in adipose tissue of tumor-free breasts clearly differed from that of cancer-bearing breasts. We observed 81 genes significantly differentially expressed between the two groups. Among the overexpressed genes were the previously identified genes MARCO and VSIG4, which were 1.5-fold upregulated in adipose tissue from diseased patients (both p-value = 0.001). Both genes are involved in processes of immunity and inflammation, promoting immune-tolerance in macrophages and T-cells. Other differentially expressed genes also relate to these pathways including CD163, CCL13 and C3. This striking role of inflammatory and immune-modulatory processes was further supported by pathway analyses.
Conclusions
Breast adipose tissues of cancer-bearing breasts show distinct gene expression profiles from that of tumor-free breasts, whereas tumor-distant and tumor-close adipose tissues are similar. However the selected distance of ≤2cm from the tumor may by insufficient to capture the tumor micro-environment. Nevertheless, this rather provocative result raises issues related to the status of breast adipose tissue that may define individually determined cancer fields. Differentially expressed genes are, to a large proportion, involved in immunity-related and inflammatory processes, emphasizing that adipose tissue is an important contributor to one of the hallmarks of cancer.
Citation Format: Dominique Scherer, Isabelle Miran, Chafika Mazouni, Benjamin Sarfati, Marine Bernard, Julien Adam, Emilie Louvet, Francoise Drusch, Philippe Vielh, Khalid Alhazmi, Cornelia M. Ulrich, Suzette Delaloge, Jean Feunteun. Gene expression profiles in adipose tissue of cancer-bearing breasts differ from that of tumor-free breasts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4286.