Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

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

Naturvetenskap

Natural sciences

Bioinformatik

Bioinformatics

Medicin

Publikations- och innehållstyp

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