PD-L1 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy
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Heidrun Gevensleben1,*, Emily Eva Holmes1,*, Diane Goltz1,*, Jörn Dietrich2, Verena Sailer3,4, Jörg Ellinger5, Dimo Dietrich1,2,**, Glen Kristiansen1,**
1Institute of Pathology, University Hospital Bonn, Bonn, Germany
2Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany
3Weill Cornell Medicine of Cornell University, Department of Pathology and Laboratory Medicine, New York, NY, USA
4Weill Cornell Medicine of Cornell University, Englander Institute for Precision Medicine, New York, NY, USA
5Department of Urology, University Hospital Bonn, Bonn, Germany
*These authors have contributed equally to this work
**These authors are joint senior authors of this work
Dimo Dietrich, email: email@example.com
Keywords: PD-L1, prostate cancer, DNA methylation, prognostic biomarker
Received: August 05, 2016 Accepted: October 13, 2016 Published: November 07, 2016
Background: The rapid development of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has generated an urgent need for biomarkers assisting the selection of patients eligible for therapy. The use of PD-L1 immunohistochemistry, which has been suggested as a predictive biomarker, however, is confounded by multiple unresolved issues. The aim of this study therefore was to quantify PD-L1 DNA methylation (mPD-L1) in prostate tissue samples and to evaluate its potential as a biomarker in prostate cancer (PCa).
Results: In the training cohort, normal tissue showed significantly lower levels of mPD-L1 compared to tumor tissue. High mPD-L1 in PCa was associated with biochemical recurrence (BCR) in univariate Cox proportional hazards (hazard ratio (HR)=2.60 [95%CI: 1.50-4.51], p=0.001) and Kaplan-Meier analyses (p<0.001). These results were corroborated in an independent validation cohort in univariate Cox (HR=1.24 [95%CI: 1.08-1.43], p=0.002) and Kaplan-Meier analyses (p=0.029). Although mPD-L1 and PD-L1 protein expression did not correlate in the validation cohort, both parameters added significant prognostic information in bivariate Cox analysis (HR=1.22 [95%CI: 1.05-1.42], p=0.008 for mPD-L1 and HR=2.58 [95%CI: 1.43-4.63], p=0.002 for PD-L1 protein expression).
Methods: mPD-L1 was analyzed in a training cohort from The Cancer Genome Atlas (n=498) and was subsequently measured in an independent validation cohort (n=299) by quantitative methylation-specific real-time PCR. All patients had undergone radical prostatectomy.
Conclusions: mPD-L1 is a promising biomarker for the risk stratification of PCa patients and might offer additional relevant prognostic information to the implemented clinical parameters, particularly in the setting of immune checkpoint inhibition.
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