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A miRNA expression signature that separates between normal and malignant prostate tissues
Örebro University, School of Health and Medical Sciences. (Tumörbiologi, Bioinformatik)ORCID iD: 0000-0001-5533-7899
Örebro University, School of Health and Medical Sciences.
Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0003-2317-5738
Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0001-6881-237X
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2011 (English)In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, no 11, p. 14-Article in journal (Refereed) Published
Abstract [en]

Background

MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that post-transcriptionally regulate genes involved in several key biological processes and thus are involved in various diseases, including cancer. In this study we aimed to identify a miRNA expression signature that could be used to separate between normal and malignant prostate tissues.

Results

Nine miRNAs were found to be differentially expressed (p <0.00001). With the exception of two samples, this expression signature could be used to separate between the normal and malignant tissues. A cross-validation procedure confirmed the generality of this expression signature. We also identified 16 miRNAs that possibly could be used as a complement to current methods for grading of prostate tumor tissues.

Conclusions

We found an expression signature based on nine differentially expressed miRNAs that with high accuracy (85%) could classify the normal and malignant prostate tissues in patients from the Swedish Watchful Waiting cohort. The results show that there are significant differences in miRNA expression between normal and malignant prostate tissue, indicating that these small RNA molecules might be important in the biogenesis of prostate cancer and potentially useful for clinical diagnosis of the disease.

Place, publisher, year, edition, pages
BioMed Central, 2011. no 11, p. 14-
National Category
Natural Sciences Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-25828DOI: 10.1186/1475-2867-11-14ISI: 000292110200001PubMedID: 21619623OAI: oai:DiVA.org:oru-25828DiVA, id: diva2:552279
Available from: 2012-09-17 Created: 2012-09-13 Last updated: 2018-05-04Bibliographically 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. p. 55
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 74
Keywords
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: 2017-10-17Bibliographically approved

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Carlsson, JessicaDavidsson, SabinaHelenius, GiselaKarlsson, MatsAndrén, Ove

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