title: miRNAs can predict prostate cancer biochemical relapse and are involved in tumor progression.
abstract: Prostate cancer is the leading cancer diagnosed and the second most common cause of cancer related death in the western world. For prognostic monitoring after prostatectomy, recurrent increase of prostate-specific antigen (PSA), the so-called PSA or biochemical relapse remains the leading biomarker. There is currently no biomarker that can accurately predict the risk of relapse at the time of surgery. We analyzed formalin-fixed and paraffin-embedded tissue samples from 52 primary prostate cancers and normal adjacent tissues obtained after radical prostatectomy. Patients were grouped into two categories: i) patients with early biochemical relapse (<1 year after radical prostatectomy) and ii) patients with late or no biochemical relapse (>2 years after surgery). Multiplex real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed to identify a miRNA signature that can predict relapse. Results were validated by quantitative RT-PCR analysis. We identified 63 miRNAs that were differentially expressed among the same categories of patients, of whom 35 miRNAs were up-regulated and 28 were down-regulated. Literature search shows that many of these miRNAs have an established prognostic significance in other cancers and can be actively involved in tumor progression. Target prediction analysis showed that predicted targets of these miRNAs could be involved in biological processes and pathways that enhance tumor progression. We experimentally validated the role of one of the dysregulated miRNAs (miR-10b) in relapse using proliferation and wound-healing assay. miRNAs can be reliable predictive markers for biochemical relapse of prostate cancer at the time of radical prostatectomy. This should have significant impact on patient managing plans.
authors.affiliation: Department of Biology, Chemistry and Pharmacy, Free University, Berlin, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Fendler
authors.forename: Monika
authors.initials: M
authors.lastname: Jung
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.forename: Richardson J
authors.initials: RJ
authors.lastname: Honey
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Stewart
authors.forename: Kenneth T
authors.initials: KT
authors.lastname: Pace
authors.forename: Andreas
authors.initials: A
authors.lastname: Erbersdobler
authors.forename: Sara
authors.initials: S
authors.lastname: Samaan
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: George M
authors.initials: GM
authors.lastname: Yousef
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012008:Recurrence
chemical_list: D014408:Biomarkers, Tumor; C547183:MIRN10 microRNA, human; D035683:MicroRNAs