title: Promoter methylation of the immune checkpoint receptorPD-1(PDCD1) is an independent prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy.
abstract: Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study,PD-1(PDCD1) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn. In the TCGA cohort, thePD-1promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs. 38.2%,p< 0.001) andPD-1methylation (mPD-1) inversely correlated with PD-1 mRNA expression in PCa (Spearman's ρ = -0.415,p< 0.001). In both cohorts,mPD-1significantly correlated with preoperative prostate specific antigen (PSA). In univariate Cox Proportional Hazard analysis,mPD-1served as a significant prognostic factor for biochemical recurrence (BCR)-free survival (Hazard ratio: HR = 2.35 [1.35-4.10],p= 0.003, n = 410) in the TCGA cohort. In multivariate analysis,mPD-1was shown to add significant independent prognostic information adjunct to pathologic tumor category (pT) and Gleason grading group (HR = 2.08 [1.16-3.74],p= 0.014, n = 350).PD-1promoter methylation analyses could thus potentially aid the identification of patients which might benefit from adjuvant treatment after radical prostatectomy. Moreover, our data suggest an intrinsic role of PD-1 in PCa carcinogenesis and disease progression, which needs to be addressed in future studies.
authors.affiliation: Institute of Pathology, University Hospital Bonn , Bonn, Germany.
authors.forename: Diane
authors.initials: D
authors.lastname: Goltz
authors.affiliation: Institute of Pathology, University Hospital Bonn , Bonn, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Gevensleben
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn , Bonn, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Dietrich
authors.affiliation: Department of Urology, University Hospital Bonn , Bonn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.affiliation: Department of Dermatology, University Hospital Bonn , Bonn, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Landsberg
authors.affiliation: Institute of Pathology, University Hospital Bonn , Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany; Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany.
authors.forename: Dimo
authors.initials: D
authors.lastname: Dietrich
keywords: DNA methylation; PD-1; PDCD1; prognostic biomarker; prostate cancer