title: MiRNA Profiles in Lymphoblastoid Cell Lines of Finnish Prostate Cancer Families.
abstract: BACKGROUND
  Heritable factors are evidently involved in prostate cancer (PrCa) carcinogenesis, but currently, genetic markers are not routinely used in screening or diagnostics of the disease. More precise information is needed for making treatment decisions to distinguish aggressive cases from indolent disease, for which heritable factors could be a useful tool. The genetic makeup of PrCa has only recently begun to be unravelled through large-scale genome-wide association studies (GWAS). The thus far identified Single Nucleotide Polymorphisms (SNPs) explain, however, only a fraction of familial clustering. Moreover, the known risk SNPs are not associated with the clinical outcome of the disease, such as aggressive or metastasised disease, and therefore cannot be used to predict the prognosis. Annotating the SNPs with deep clinical data together with miRNA expression profiles can improve the understanding of the underlying mechanisms of different phenotypes of prostate cancer.
  
  
  RESULTS
  In this study microRNA (miRNA) profiles were studied as potential biomarkers to predict the disease outcome. The study subjects were from Finnish high risk prostate cancer families. To identify potential biomarkers we combined a novel non-parametrical test with an importance measure provided from a Random Forest classifier. This combination delivered a set of nine miRNAs that was able to separate cases from controls. The detected miRNA expression profiles could predict the development of the disease years before the actual PrCa diagnosis or detect the existence of other cancers in the studied individuals. Furthermore, using an expression Quantitative Trait Loci (eQTL) analysis, regulatory SNPs for miRNA miR-483-3p that were also directly associated with PrCa were found.
  
  
  CONCLUSIONS
  Based on our findings, we suggest that blood-based miRNA expression profiling can be used in the diagnosis and maybe even prognosis of the disease. In the future, miRNA profiling could possibly be used in targeted screening, together with Prostate Specific Antigene (PSA) testing, to identify men with an elevated PrCa risk.
authors.affiliation: School of Health Sciences, University of Tampere, 33014 Tampere, Finland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fischer
authors.affiliation: BioMediTech, University of Tampere, and Fimlab Laboratories, Tampere, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Wahlfors
authors.affiliation: BioMediTech, University of Tampere, and Fimlab Laboratories, Tampere, Finland.
authors.forename: Henna
authors.initials: H
authors.lastname: Mattila
authors.affiliation: Department of Mathematics and Statistics, University of Turku, 20014 Turku, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Oja
authors.affiliation: Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland.
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.affiliation: Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schleutker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002460:Cell Line; D005190:Family; D005387:Finland; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D040641:Quantitative Trait Loci; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics
chemical_list: C548912:MIRN483 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm