Epigenomic Deconvolution of Breast Tumors Reveals Metabolic Coupling between Constituent Cell Types

Abstract

Cancer progression depends on both cell-intrinsic processes and interactions between different cell types. However, large-scale assessment of cell type composition and molecular profiles of individual cell types within tumors remains challenging. To address this, we developed epigenomic deconvolution (EDec), an in silico method that infers cell type composition of complex tissues as well as DNA methylation and gene transcription profiles of constituent cell types. By applying EDec to The Cancer Genome Atlas (TCGA) breast tumors, we detect changes in immune cell infiltration related to patient prognosis, and a striking change in stromal fibroblast-to-adipocyte ratio across breast cancer subtypes. Furthermore, we show that a less adipose stroma tends to display lower levels of mitochondrial activity and to be associated with cancerous cells with higher levels of oxidative metabolism. These findings highlight the role of stromal composition in the metabolic coupling between distinct cell types within tumors.

Keywords: DNA methylation; Warburg effect; breast cancer; cancer; cell type composition; deconvolution; gene expression; heterotypic interaction; metabolic coupling; metabolism.