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Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. (Tumörbiologi, Bioinformatik)ORCID iD: 0000-0001-5533-7899
Universitetssjukhuset Örebro.
Universitetssjukhuset Örebro.
Universitetssjukhuset Örebro.
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(English)Manuscript (preprint) (Other academic)
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 to the difference in propensity of tumors in the zones of the prostate.

Methods:

The expression of 667 unique miRNAs was investigated in normal and malignant transition zone and peripheral zone prostate tissues using TaqMan low density arrays for miRNAs. Student’s t-test was used in order to identify differentially expressed miRNAs and hierarchical clustering and principal component analyses were used to note the separation of the tissues. A cross-validation test using the ADtree algorithm was used to test the generality of the identified miRNA signatures.

Results:

The Student’s t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentiallyexpressed miRNAs between normal and malignant tissues showed a perfect separation between samples while analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmedt hese results and several potential miRNA markers were identified.

Conclusions:

The results of this study indicate that the major differences in the transcription programme are those arising during tumor development, rather than during normal tissue development. In conclusion, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ, indicating that the PZ are more prone to tumor development than the TZ. The results also indicate that separate miRNA expression signatures for diagnosis might be needed for tumors arising in the transition- or peripheral zone.

National Category
Medical and Health Sciences Natural Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-25829OAI: oai:DiVA.org:oru-25829DiVA: diva2:552281
Available from: 2012-09-17 Created: 2012-09-13 Last updated: 2016-11-30Bibliographically approved
In thesis
1. Identification of miRNA expression profiles for diagnosis and prognosis of prostate cancer
Open this publication in new window or tab >>Identification of miRNA expression profiles for diagnosis and prognosis of prostate cancer
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cancer of the prostate (CaP) is the most common malignancy diagnosed in men in the Western society. During the last years, prostate specific antigen (PSA) has been used as a biomarker for CaP, although a high PSA value is not specific for CaP. Thus, there is an urgent need for new and improved diagnostic markers for CaP.

In this thesis, the aim was to find a miRNA signature for diagnosis of CaP and to elucidate if differences in behavior between transition zone and peripheral zone tumors are reflected in miRNA expression. One of the major findings is anexpression signature based on nine miRNAs that with high accuracy (85%) could classify normal and malignant tissues from the transition zone of the prostate. The results furthermore show that the major differences in miRNA expression are found between normal and malignant tissues, rather than between the different zones. In addition, tumors arising in the peripheral zone have fewer changes in miRNA expression compared to tumors in the transition zone, indicating that the peripheral zone is more prone to tumor development compared to the transition zone of the prostate.

A crucial step in pre-processing of expression data, in order to differentiate true biological changes, is the normalization step. Therefore, an additional aim of this thesis was to compare different normalization methods for qPCR array data in miRNA expression experiments. The results show that data-driven methods based on quantile normalization performs the best. The results also show that in smaller miRNA expression studies, only investigating a few miRNAs, RNU24 is the most suitable endogenous control gene for normalization.

Taken together, the results in this thesis show the importance of miRNAs and the possibility of their future use as biomarkers in the field of prostate cancer.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2012. 55 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 74
Keyword
Prostate cancer, microRNAs, prostate zones, normalization, endogenous controls
National Category
Medical and Health Sciences Cancer and Oncology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-25600 (URN)978-91-7668-888-5 (ISBN)
Public defence
2012-10-26, Wilandersalen, Universitetssjukuset (USÖ), Örebro, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2012-08-30 Created: 2012-08-30 Last updated: 2016-12-06Bibliographically approved

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