title: KDM5C is overexpressed in prostate cancer and is a prognostic marker for prostate-specific antigen-relapse following radical prostatectomy.
abstract: Currently, few prognostic factors are available to predict the emergence of castration-resistant prostate cancer and no curative options are available. Epigenetic gene regulation has been shown to trigger prostate cancer metastasis and androgen independence. Histone lysine demethylases (KDMs) are epigenetic enzymes that can remove both repressive and activating histone marks. KDM5 family members are capable of removing the histone H3 lysine 4 dimethylation-activating mark, rendering them potential players in the down-regulation of tumor suppressors and suggesting that their activity could repress oncogenes. Here, we systematically investigated KDM5C expression patterns in two independent radical prostatectomy cohorts (822 prostate tumors in total) by immunohistochemistry. Positive nuclear KDM5C staining was significantly associated with a reduced prostate-specific antigen relapse-free survival. Our study confirmed that nuclear KDM5C expression is an independent prognostic parameter. Most strikingly, the prognostic value of nuclear KDM5C expression for progression-free survival was exclusively pronounced for the Gleason group 7. In addition, KDM5C knockdown resulted in growth retardation of prostate cancer cells in vitro and induced regulation of several proliferation-associated genes. Our data indicate that KDM5C is functionally involved in proliferation control of prostate cancer cells and might represent a novel attractive therapy target. Moreover, overexpression of KDM5C is an independent new predictive marker for therapy failure as determined by biochemical recurrence in patients after prostatectomy.
authors.affiliation: Institute of Pathology, University of Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Stein
authors.affiliation: Institute of Pathology, University of Bonn, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Majores
authors.affiliation: Institute of Pathology, University of Bonn, Bonn, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Institute of Pathology, University of Cologne, Köln, Germany.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Lim
authors.affiliation: Institute of Pathology, University of Bonn, Bonn, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Institute of Pathology, University of Bonn, Bonn, Germany.
authors.forename: Eliana
authors.initials: E
authors.lastname: Krappe
authors.affiliation: Department of Urology, University of Bonn, Bonn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.affiliation: Institute of Pathology, Charité University Hospital, Berlin, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.affiliation: Department of Urology, Charité University Hospital, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.affiliation: Berlin Institute of Urologic Research, Charité University Hospital, Berlin, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.affiliation: Institute of Pathology, University of Bonn, Bonn, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.affiliation: Institute of Pathology, University of Bonn, Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Institute of Pathology, University of Bonn, Bonn, Germany. Electronic address: jutta.kirfel@ukb.uni-bonn.de.
authors.forename: Jutta
authors.initials: J
authors.lastname: Kirfel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D056466:Histone Demethylases; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D056466:Histone Demethylases; C086877:KDM5C protein, human; D010089:Oxidoreductases, N-Demethylating; D017430:Prostate-Specific Antigen