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

作者：Kristensen Helle; Thomsen Anni R; Haldrup Christa; Dyrskjot Lars; Hoyer Soren; Borre Michael; Mouritzen Peter; Orntoft Torben F; Sorensen Karina Dalsgaard^*

来源：Oncotarget, 2016, 7(21): 30760-30771.

DOI：10.16632/oncotarget.8953

• prostate cancer
• biomarker
• diagnosis
• prognosis
• microRNA

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.

• 出版日期2016-5-24