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Molecular differences in transition zone and peripheral zone prostate tumors
Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Biostatistics, Harvard School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
Department of Epidemiology, Harvard School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.ORCID iD: 0000-0001-5533-7899
Department of Epidemiology, College of Medicine and College of Public Health and Health Professions, University of Florida, Gainesville, USA.
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2015 (English)In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 36, no 6, 632-638 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Oxford University Press, 2015. Vol. 36, no 6, 632-638 p.
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-44588DOI: 10.1093/carcin/bgv051ISI: 000356181700004PubMedID: 25870172OAI: oai:DiVA.org:oru-44588DiVA: diva2:811688
Funder
NIH (National Institute of Health), CA34944 CA40360 CA097193 HL26490 HL34595 UM1 CA167552 R01 HL35464 GM074897 CA09001 CA141298 CA136578 CA090381Swedish Cancer Society, CAN 2013/650
Note

Funding Agencies:

Swedish Cancer Foundation

Örebro County Council Research Foundation

A. David Mazzone Career Development Award

Örebro University

Prostate Cancer Foundation

Available from: 2015-05-12 Created: 2015-05-11 Last updated: 2015-07-21Bibliographically approved

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Carlsson, JessicaFall, KatjaAndersson, Sven-OlofAndrén, Ove
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