Title | PD-L1 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Gevensleben H, Holmes EEva, Goltz D, Dietrich J, Sailer V, Ellinger J, Dietrich D, Kristiansen G |
Journal | Oncotarget |
Volume | 7 |
Issue | 48 |
Pagination | 79943-79955 |
Date Published | 2016 Nov 29 |
ISSN | 1949-2553 |
Keywords | B7-H1 Antigen, Biomarkers, Tumor, Disease-Free Survival, DNA Methylation, Follow-Up Studies, Humans, Male, Middle Aged, Predictive Value of Tests, Prognosis, Promoter Regions, Genetic, Prostatectomy, Prostatic Neoplasms, Treatment Outcome |
Abstract | 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. |
DOI | 10.18632/oncotarget.13161 |
Alternate Journal | Oncotarget |
PubMed ID | 27835597 |
PubMed Central ID | PMC5346762 |