Molecular differences in transition zone and peripheral zone prostate tumors.

TitleMolecular differences in transition zone and peripheral zone prostate tumors.
Publication TypeJournal Article
Year of Publication2015
AuthorsSinnott JA, Rider JR, Carlsson J, Gerke T, Tyekucheva S, Penney KL, Sesso HD, Loda M, Fall K, Stampfer MJ, Mucci LA, Pawitan Y, Andersson S-O, Andrén O
JournalCarcinogenesis
Volume36
Issue6
Pagination632-8
Date Published2015 Jun
ISSN1460-2180
KeywordsBiomarkers, Tumor, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Prognosis, Prostate, Prostatic Neoplasms
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.

DOI10.1093/carcin/bgv051
Alternate JournalCarcinogenesis
PubMed ID25870172
PubMed Central IDPMC4572920
Grant ListHL34595 / HL / NHLBI NIH HHS / United States
CA34944 / CA / NCI NIH HHS / United States
CA141298 / CA / NCI NIH HHS / United States
GM074897 / GM / NIGMS NIH HHS / United States
T32 GM074897 / GM / NIGMS NIH HHS / United States
CA097193 / CA / NCI NIH HHS / United States
R01HL35464 / HL / NHLBI NIH HHS / United States
CA090381 / CA / NCI NIH HHS / United States
CA40360 / CA / NCI NIH HHS / United States
P50 CA090381 / CA / NCI NIH HHS / United States
R35 CA197449 / CA / NCI NIH HHS / United States
CA136578 / CA / NCI NIH HHS / United States
HL26490 / HL / NHLBI NIH HHS / United States
UM1 CA167552 / CA / NCI NIH HHS / United States
CA09001 / CA / NCI NIH HHS / United States
Related Faculty: 
Massimo Loda, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
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