Abstract P3-03-12: Obesity promotes the activation of genes and pathways in tumor associated breast fat

Tumor-associated adipocytes play an active role in breast tumor progression. Moreover, obesity has been established as a risk factor in cancer-related mortality. The altered expression of genes and signaling pathways in breast adipose as a result of obesity may create a more favorable microenvironment for tumor progression. To this end, we analyzed transcriptome profiles of human adipose tissue from lean and obese women with invasive breast cancer using RNA sequencing (n=10/group). Within individuals, adipose tissue was sampled proximal and distal (2 cm) to the breast tumor. A heat map of normalized expression values was generated with unsupervised clustering for the most informative genes. A cluster heat map was obtained by the analysis of the express of 35 DEGs with the most significant differences (adjusted p-value P 2) recorded. Starting with a list of genes marked as significant in the analysis of lean vs obese, we queried the STRING database. Using ClusterMaker2 and MCL clustering, we performed enrichment analysis and found KEGG pathway hsa05224 breast cancer was enriched with an FDR of 2.7e-40. Using KEGGParser, we over-layed fold changes from lean vs obese data. In examining obese women, there were 16 Hallmark pathways that were statistically significant (adjusted p-value P Citation Format: Niel Infante, James Coad, Don Primerano, James Denvir, Linda Vona-Davis. Obesity promotes the activation of genes and pathways in tumor associated breast fat [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-03-12.