title: The combined serum levels of miR-375 and urokinase plasminogen activator receptor are suggested as diagnostic and prognostic biomarkers in prostate cancer.
abstract: This study aimed to assess the applicability of miR-375 in combination with the soluble urokinase plasminogen activator receptor (suPAR) protein as a diagnostic and/or prognostic biomarker for prostate cancer (PCa) patients. miR-375 levels by qRT-PCR and suPAR levels by ELISA were evaluated in serum samples from 146 PCa patients, 35 benign prostate hyperplasia (BPH) patients and 18 healthy controls. Antigen levels of suPAR differed between healthy controls and PCa or BPH patients, whereas miR-375 levels differed between PCa and BPH patients or healthy controls (p < 0.001). Additionally, suPAR levels differed between the Gleason sum groups GS = 7 versus GS > 7, with higher levels in the latter group (p = 0.011), and miR-375 levels were higher in the tumor stage group T3-T4 compared with the T1-T2 group (p = 0.039). A high concentration of suPAR was associated with a poor disease-specific survival (DSS; p = 0.039). The combination of suPAR and miR-375 levels identified a patient group possessing high levels for both parameters. This was associated with a poorer 10-year overall survival (OS) and DSS, with a 6.38-fold increased risk of death and a 7.68-fold increased risk of tumor-related death (p = 0.00026 and p = 0.014; univariate Cox's regression analysis). In a multivariate Cox's regression analysis PCa patients with high levels of suPAR and miR-375 showed a 5.72-fold increased risk of death in OS (p = 0.006). In summary, the differences between the PCa/BPH/healthy control cohorts for either suPAR and miR-375 levels in conjunction with the association of combined high suPAR/miR-375 levels with a poor prognosis suggest a diagnostic and prognostic impact for PCa patients.
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Wach
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Omar
authors.initials: O
authors.lastname: Al-Janabi
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Weigelt
authors.affiliation: Department of Urology, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Kersten
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Center for Reproductive Medicine and Andrology, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Greither
authors.affiliation: Department of Urology, Martin Luther University Halle-Wittenberg, Halle, Germany.|Center for Reproductive Medicine and Andrology, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Marios
authors.initials: M
authors.lastname: Marcou
authors.affiliation: Department of Urology, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Gerit
authors.initials: G
authors.lastname: Theil
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Nolte
authors.affiliation: Institute of Pathology, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Holzhausen
authors.affiliation: Institute of Pathology, Universitätsklinikum Erlangen, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Stöhr
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Huppert
authors.affiliation: Institute of Pathology, Universitätsklinikum Erlangen, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Department of Urology, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fornara
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D012306:Risk; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D055293:Receptors, Urokinase Plasminogen Activator
keywords: diagnosis; disease-specific survival; miR-375; overall survival; prostate cancer; urokinase plasminogen activator receptor