Novel diagnostic and prognostic classifiers for prostate cancer identified by genome-wide microRNA profiling

Helle Kristensen; Anni R. Thomsen; Christa Haldrup; Lars Dyrskjøt; Søren Høyer; Michael Borre; Peter Mouritzen; Torben F. Ørntoft; Karina Dalsgaard Sørensen

doi:10.18632/oncotarget.8953

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Research Papers:

Novel diagnostic and prognostic classifiers for prostate cancer identified by genome-wide microRNA profiling

Helle Kristensen, Anni R. Thomsen, Christa Haldrup, Lars Dyrskjøt, Søren Høyer, Michael Borre, Peter Mouritzen, Torben F. Ørntoft and Karina Dalsgaard Sørensen _

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Oncotarget. 2016; 7:30760-30771. https://doi.org/10.18632/oncotarget.8953

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Abstract

Helle Kristensen1,2, Anni R. Thomsen2, Christa Haldrup1, Lars Dyrskjøt1, Søren Høyer3, Michael Borre4, Peter Mouritzen2, Torben F. Ørntoft1, Karina Dalsgaard Sørensen1

1Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark

2Exiqon A/S, Skelstedet, Vedbaek, Denmark

3Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark

4Department of Urology, Aarhus University Hospital, Aarhus, Denmark

Correspondence to:

Karina Dalsgaard Sørensen, email: [email protected]

Keywords: prostate cancer, biomarker, diagnosis, prognosis, microRNA

Received: January 14, 2016 Accepted: April 02, 2016 Published: April 23, 2016

ABSTRACT

Purpose: This study investigates the diagnostic and prognostic biomarker potential of miRNAs in prostate cancer (PC).

Results: We identified several new deregulated miRNAs between non-malignant (NM) and PC tissue samples and between more/less aggressive PC subgroups. We also developed and validated a novel 13-miRNA diagnostic classifier with high sensitivity and specificity for PC. Finally, we trained a new 3-miRNA prognostic classifier (miR-185-5p+miR-221-3p+miR-326) that predicted time to biochemical recurrence (BCR) independently of routine clinicopathological variables in a training radical prostatectomy (RP) cohort (n = 126) as well as in two independent validation cohorts (n = 110 and n = 99).

Experimental Design: After RT-qPCR-based profiling of 752 miRNAs in 13 NM and 134 PC tissue samples (cohort 1), we selected 93 top candidate diagnostic/prognostic miRNAs for validation in two independent patient sets (cohort 2: 19 NM and 138 PC; cohort 3: 28 NM and 113 PC samples). Diagnostic potential was assessed by ROC curve analysis and prognostic potential by Kaplan-Meier, uni- and multivariate Cox regression analyses. BCR after RP was used as endpoint.

Conclusions: This is the first report of a miRNA signature with significant independent prognostic value demonstrated in three PC patient cohorts.

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Research Papers:

Novel diagnostic and prognostic classifiers for prostate cancer identified by genome-wide microRNA profiling

Abstract