PD-L1 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy.
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.
Institute of Pathology, University Hospital Bonn, Bonn, Germany.
Heidrun
H
Gevensleben
Institute of Pathology, University Hospital Bonn, Bonn, Germany.
Emily Eva
EE
Holmes
Institute of Pathology, University Hospital Bonn, Bonn, Germany.
Diane
D
Goltz
Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany.
Jörn
J
Dietrich
Weill Cornell Medicine of Cornell University, Department of Pathology and Laboratory Medicine, New York, NY, USA.|Weill Cornell Medicine of Cornell University, Englander Institute for Precision Medicine, New York, NY, USA.
Verena
V
Sailer
Department of Urology, University Hospital Bonn, Bonn, Germany.
Jörg
J
Ellinger
Institute of Pathology, University Hospital Bonn, Bonn, Germany.|Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany.
Dimo
D
Dietrich
Institute of Pathology, University Hospital Bonn, Bonn, Germany.
Glen
G
Kristiansen
D060890:B7-H1 Antigen / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery*; D016896:Treatment Outcome
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
DNA methylation; PD-L1; prognostic biomarker; prostate cancer