title: Molecular differences in transition zone and peripheral zone prostate tumors.
abstract: Prostate tumors arise primarily in the peripheral zone (PZ) of the prostate, but 20-30% arise in the transition zone (TZ). Zone of origin may have prognostic value or reflect distinct molecular subtypes; however, it can be difficult to determine in practice. Using whole-genome gene expression, we built a signature of zone using normal tissue from five individuals and found that it successfully classified nine tumors of known zone. Hypothesizing that this signature captures tumor zone of origin, we assessed its relationship with clinical factors among 369 tumors of unknown zone from radical prostatectomies (RPs) and found that tumors that molecularly resembled TZ tumors showed lower mortality (P = 0.09) that was explained by lower Gleason scores (P = 0.009). We further applied the signature to an earlier study of 88 RP and 333 transurethral resection of the prostate (TURP) tumor samples, also of unknown zone, with gene expression on ~6000 genes. We had observed previously substantial expression differences between RP and TURP specimens, and hypothesized that this might be because RPs capture primarily PZ tumors, whereas TURPs capture more TZ tumors. Our signature distinguished these two groups, with an area under the receiver operating characteristic curve of 87% (P < 0.0001). Our findings that zonal differences in normal tissue persist in tumor tissue and that these differences are associated with Gleason score and sample type suggest that subtypes potentially resulting from different etiologic pathways might arise in these zones. Zone of origin may be important to consider in prostate tumor biomarker research.
authors: Department of Epidemiology and Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors: Jennifer A
authors: JA
authors: Sinnott
authors: Department of Epidemiology and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, rider@hsph.harvard.edu.
authors: Jennifer R
authors: JR
authors: Rider
authors: Department of Urology, School of Health and Medical Sciences, University of Orebro, Orebro 701 85, Sweden.
authors: Jessica
authors: J
authors: Carlsson
authors: Department of Epidemiology, College of Medicine and College of Public Health and Health Professions, University of Florida, Gainesville, FL 32611, USA.
authors: Travis
authors: T
authors: Gerke
authors: Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors: Svitlana
authors: S
authors: Tyekucheva
authors: Department of Epidemiology and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors: Kathryn L
authors: KL
authors: Penney
authors: Department of Epidemiology and Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors: Howard D
authors: HD
authors: Sesso
authors: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors: Massimo
authors: M
authors: Loda
authors: Department of Epidemiology and Department of Clinical Epidemiology and Biostatistics, School of Health and Medical Sciences, Orebro University, Orebro 701 85, Sweden and.
authors: Katja
authors: K
authors: Fall
authors: Department of Epidemiology and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors: Meir J
authors: MJ
authors: Stampfer
authors: Department of Epidemiology and.
authors: Lorelei A
authors: LA
authors: Mucci
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm 171 77, Sweden.
authors: Yudi
authors: Y
authors: Pawitan
authors: Department of Urology, School of Health and Medical Sciences, University of Orebro, Orebro 701 85, Sweden.
authors: Sven-Olof
authors: SO
authors: Andersson
authors: Department of Urology, School of Health and Medical Sciences, University of Orebro, Orebro 701 85, Sweden.
authors: Ove
authors: O
authors: Andrén
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D011379:Prognosis; D011467:Prostate / Q000033:anatomy & histology* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor