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Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate
Örebro University / Örebro University Hospital.
Örebro University / Örebro University Hospital.
Örebro University / Örebro University Hospital.
Örebro University / Örebro University Hospital.
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2013 (English)In: BMC Cancer, ISSN 1471-2407, Vol. 13, 362Article in journal (Refereed) Published
Abstract [en]

Background: The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate. Methods: Patients with prostate cancer were included in the study if they had a tumor with Gleason grade 3 in the PZ, the TZ, or both (n=16). Normal prostate tissue was collected from men undergoing cystoprostatectomy (n=20). The expression of 667 unique miRNAs was investigated using TaqMan low density arrays for miRNAs. Student's t-test was used in order to identify differentially expressed miRNAs, followed by hierarchical clustering and principal component analysis (PCA) to study the separation of the tissues. The ADtree algorithm was used to identify markers for classification of tissues and a cross-validation procedure was used to test the generality of the identified miRNA-based classifiers. Results: The t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentially expressed miRNAs between normal and malignant tissues showed perfect separation between samples, while the corresponding analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmed these results and several potential miRNA markers were identified. Conclusions: The results of this study indicate that the major differences in the transcription program are those arising during tumor development, rather than during normal tissue development. In addition, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ. The results also indicate that separate miRNA expression signatures for diagnosis might be needed for tumors arising in the different zones. MicroRNA signatures that are specific for PZ and TZ tumors could also lead to more accurate prognoses, since tumors arising in the PZ tend to be more aggressive than tumors arising in the TZ.

Place, publisher, year, edition, pages
BioMed Central, 2013. Vol. 13, 362
Keyword [en]
MiRNA expression, Prostate cancer, Prostate zones, microRNA, microRNA 127 3p, microrna 154, microRNA 15a, microRNA 15b, microRNA 181c, microRNA 216b, microRNA 22, microRNA 27b, microRNA 337 3p, microrna 379, microRNA 424, microRNA 433, microrna 494, microRNA 495, microRNA 543, phosphatidylinositol 3, 4, 5 trisphosphate 3 phosphatase, transforming growth factor beta, unclassified drug, adult, aged, article, cancer grading, cell cycle arrest, cell cycle regulation, central zone, clinical article, controlled study, gene expression, gene function, gene targeting, human, human tissue, male, pathogenesis, peripheral zone, prostate, tissue differentiation, transition zone
National Category
Natural Sciences
Research subject
Natural sciences
URN: urn:nbn:se:his:diva-8710DOI: 10.1186/1471-2407-13-362ISI: 000322598200001PubMedID: 23890084ScopusID: 2-s2.0-84880941948OAI: diva2:683140
Available from: 2014-01-02 Created: 2014-01-02 Last updated: 2015-08-13Bibliographically approved

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Klinga-Levan, KarinOlsson, Björn
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