title: MicroRNA profiles of prostate carcinoma detected by multiplatform microRNA screening.
abstract: MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via posttranscriptional inhibition of protein synthesis. They play a vital role in tumorigenesis. To characterize the diagnostic potential of miRNAs in prostate cancer, a leading cause of cancer mortality, we performed screening of miRNA expression profiles. We used commercially available microarrays to establish miRNA expression profiles from a cohort of 20 cancer samples. The expression of selected miRNAs was analyzed by quantitative real-time PCR and the identity of miRNA expressing cells was determined by miRNA in situ hybridization. We identified 25 miRNAs that showed a significant differential expression in cancer samples. The comparison with previously published data generated by deep sequencing of cDNA libraries of small RNA molecules revealed a concordance rate of 47% among miRNAs identified with both techniques. The differential expression of miRNAs miR-375, miR-143 and miR-145 was validated by quantitative PCR. MiRNA in situ hybridization revealed that the differential expression is cancer-cell associated. A combination of three miRNAs correctly classified tissue samples with an accuracy of 77.6% with an area under the receiver-operator characteristic curve of 0.810. Our data extend the knowledge about the deregulation of miRNAs in prostate cancer. The differential expression of several miRNAs is highly consistent using independent cohorts of tumor samples, different tissue preservation methods and different experimental methods. Our results indicate that combinations of miRNAs are promising biomarkers for the diagnosis of prostate cancer.
authors.affiliation: University Clinic of Urology, Friedrich-Alexander-University Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen, Germany. Sven.Wach@uk-erlangen.de
authors.forename: Sven
authors.initials: S
authors.lastname: Wach
authors.forename: Elke
authors.initials: E
authors.lastname: Nolte
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Szczyrba
authors.forename: Robert
authors.initials: R
authors.lastname: Stöhr
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Torben
authors.initials: T
authors.lastname: Ørntoft
authors.forename: Lars
authors.initials: L
authors.lastname: Dyrskjøt
authors.forename: Elke
authors.initials: E
authors.lastname: Eltze
authors.forename: Wolf
authors.initials: W
authors.lastname: Wieland
authors.forename: Bastian
authors.initials: B
authors.lastname: Keck
authors.forename: Arif B
authors.initials: AB
authors.lastname: Ekici
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grässer
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016000:Cluster Analysis; D055088:Early Detection of Cancer / Q000379:methods*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015203:Reproducibility of Results
chemical_list: D035683:MicroRNAs