title: Gene expression in local stroma reflects breast tumor states and predicts patient outcome.
abstract: 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.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Russell
authors.initials: R
authors.lastname: Bainer
authors.affiliation: Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Frankenberger
authors.affiliation: Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rabe
authors.affiliation: Department of Surgery, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: An
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gilad
authors.affiliation: Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Marsha Rich
authors.initials: MR
authors.lastname: Rosner
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012334:RNA, Neoplasm / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D017423:Sequence Analysis, RNA; D017154:Stromal Cells / Q000378:metabolism*; D015996:Survival Rate; D014183:Transplantation, Heterologous
chemical_list: D015820:Cadherins; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D012334:RNA, Neoplasm