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Abstract
While progression from normal prostatic epithelium to invasive cancer is driven by molecular alterations, tumor cells and cells in the cancer microenvironment are co-dependent and co-evolve. Few human studies to date have focused on stroma. Here, we performed gene expression profiling of laser capture microdissected normal non-neoplastic prostate epithelial tissue and compared it to non-transformed and neoplastic low-grade and high-grade prostate epithelial tissue from radical prostatectomies, each with its immediately surrounding stroma. Whereas benign epithelium in prostates with and without tumor were similar in gene expression space, stroma away from tumor was significantly different from that in prostates without cancer. A stromal gene signature reflecting bone remodeling and immune-related pathways was upregulated in high compared to low-Gleason grade cases. In validation data, the signature discriminated cases that developed metastasis from those that did not. These data suggest that the microenvironment may influence prostate cancer initiation, maintenance, and metastatic progression.
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1 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
2 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
3 Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA
4 Department of Pathology, Addarii Institute of Oncology, S.Orsola-Malpighi Teaching Hospital, University of Bologna, Bologna, Italy
5 Department of Surgical Pathology, Maggiore Hospital, Bologna, Italy
6 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
7 King’s College London, Division of Cancer Studies, Translational Oncology & Urology Research, Guy’s Hospital, London, UK
8 Department of Urology, School of Health and Medical Sciences, Örebro University Hospital, Örebro, Sweden
9 School of Medicine, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
10 Department of Histopathology and Morbid Anatomy, School of Medicine, Trinity College Dublin, Dublin, Ireland
11 Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
12 Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
13 Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
14 Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; The Broad Institute, 415 Main St, Cambridge, MA, USA