Abstract 5558: Deconstruction of a human tumor microenvironment

Abstract

Abstract The purpose of this study was to understand the relationships between the molecular mechanisms of disease progression and higher-order features such as tissue stiffness, extent of disease and cellularity in the tumor microenvironment, TME. Using samples of human high-grade serous ovarian cancer metastases, ranging from normal to heavily diseased, we identified molecular components of the TME using transcriptomic and proteomic analysis. We integrated these data against higher-order features of the tissue, namely the biomechanics, cellularity, and disease score. We then used bioinformatics and multivariate statistics to identifying components of the TME that best model the higher-order features. For the first time, we revealed the complexity of extracellular matrix remodeling during metastases development, defining patterns of extracellular-matrix associated genes and proteins that predicted both extent of disease and tissue modulus. This allowed us to identify a core group of twenty-two matrix-associated molecules that modeled the dynamic process of tissue remodeling during tumor progression. We used these data to generate a ‘matrix index’, a quantitative measure of the gene expression of the twenty-two molecules. In cancer transcriptomic databases, this matrix index had prognostic significance in thirteen solid cancers including high-grade serous ovarian cancer, even after multivariate analysis. We conclude that there may be a common host matrix response to human solid cancers. Citation Format: Frances R. Balkwill, Oliver M. Pearce, Robin Delaine-Smith, Eleni Maniati, Sam Nichols, Jun Wang, Conrad Bessant, Martin Knight. Deconstruction of a human tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5558. doi:10.1158/1538-7445.AM2017-5558