Open AccessGene expression in local stroma reflects breast tumor states and predicts patient outcome
Author(s) -
Russell Bainer,
Casey Frankenberger,
Daniel C. Rabe,
Gary An,
Yoav Gilad,
Marsha Rich Rosner
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep39240
Subject(s) - stroma , stromal cell , metastasis , cancer research , breast cancer , biology , gene expression , gene , regulation of gene expression , tumor microenvironment , tumor progression , pathology , cancer , medicine , immunohistochemistry , immunology , tumor cells , genetics
The surrounding microenvironment has been implicated in the progression of breast tumors to metastasis. However, the degree to which metastatic breast tumors locally reprogram stromal cells as they disrupt tissue boundaries is not well understood. We used species-specific RNA sequencing in a mouse xenograft model to determine how the metastasis suppressor RKIP influences transcription in a panel of paired tumor and stroma tissues. We find that gene expression in metastatic breast tumors is pervasively correlated with gene expression in local stroma of both mouse xenografts and human patients. Changes in stromal gene expression elicited by tumors better predicts subtype and patient survival than tumor gene expression, and genes with coordinated expression in both tissues predict metastasis-free survival. These observations support the use of stroma-based strategies for the diagnosis and prognosis of breast cancer.