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Epigenomic deconvolution of breast tumors reveals metabolic coupling between constituent cell types

ABSTRACT: Cancer progression is dependent on both cell-intrinsic processes and interactions between different cell types that constitute tumor tissue. To access this information, we develop Epigenomic Deconvolution (EDec), an in silico method that provides estimates of cell type composition of complex tissues, such as solid tumors, as well as CpG methylation and gene transcription within constituent cell types. By applying EDec to breast tumors from TCGA we detect changes in immune cell infiltration, and a striking change in stromal fibroblast to adipocyte ratio across breast cancer subtypes. We further show that a decrease in stromal adipocyte content and increase in fibroblast content is associated with a reduction of mitochondrial activity in stromal cells and a concomitant increase in oxidative metabolism in cancerous epithelial cells. These findings highlight the role of stromal cell type composition in the establishment of patterns of metabolic coupling such as the previously proposed reverse Warburg effect. Raw data files were not provided for this Series. Submitters did not have permission to share the raw data.

ORGANISM(S): Homo sapiens

PROVIDER: GSE87297 | GEO | 2016/11/17

SECONDARY ACCESSION(S): PRJNA344072

REPOSITORIES: GEO

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