Abstract LB-357: Transcriptional Landscape of Stroma Progression in the Breast Tumor Microenvironment

Abstract The breast tumor microenvironment of primary and metastatic sites is a complex milieu of differing cell populations. However, the genomic expression landscape of the tumor stroma and its role in mediating cancer progression and informing effective therapies is not well understood. Here we obtained and cultured 52 cell-sorted stromal tissue samples across 37 patients from normal, primary tumor, and metastatic tumor sites. Deep RNA-seq was performed on poly(A)+ transcripts using a multiplexed barcoding sequencing strategy to increase yield and obviate batch effects. A conservative linear model of expression covariates revealed significant (q<0.05) differential expression of protein-coding genes and lncRNAs in the stroma (80 transcripts in normal versus primary and 108 transcripts in primary versus metastatic). The majority of these genes were found to be associated with pattern formation, embryogenesis, and the epithelial-mesenchymal transition. Among the genes that were silenced in the epithelial cells, IHC staining was initially done for C2orf88, ALOX5AP, and UNC5C which are important in PKA binding, immune response, apoptosis, and neural development. Furthermore, survival analyses of 827 luminal breast tumor samples from TCGA demonstrated the predictive power of the stromal gene expression in informing clinical outcome. Together these results highlight the evolution of stromal gene expression in breast tumors and suggest novel therapeutic strategies targeting the microenvironment. Citation Format: Raditya Utama, Anja Bastian, Narayanan Sadagopan, Ying Jin, Eric Antoniou, Yin Huang, Peter Lee, Gurinder Atwal. Transcriptional landscape of stroma progression in the breast tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-357.