Title | CXCL12 promoter methylation and PD-L1 expression as prognostic biomarkers in prostate cancer patients. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Goltz D, Holmes EEva, Gevensleben H, Sailer V, Dietrich J, Jung M, Röhler M, Meller S, Ellinger J, Kristiansen G, Dietrich D |
Journal | Oncotarget |
Volume | 7 |
Issue | 33 |
Pagination | 53309-53320 |
Date Published | 2016 Aug 16 |
ISSN | 1949-2553 |
Keywords | B7-H1 Antigen, Biomarkers, Tumor, Chemokine CXCL12, Cohort Studies, DNA Methylation, Gene Expression Regulation, Neoplastic, Humans, Kaplan-Meier Estimate, Male, Multivariate Analysis, Neoplasm Grading, Outcome Assessment, Health Care, Prognosis, Promoter Regions, Genetic, Proportional Hazards Models, Prostatectomy, Prostatic Neoplasms |
Abstract | BACKGROUND: The CXCR4/CXCL12 axis plays a central role in systemic metastasis of prostate carcinoma (PCa), thereby representing a promising target for future therapies. Recent data suggest that the CXCR4/CXCL12 axis is functionally linked to the PD-1/PD-L1 immune checkpoint. We evaluated the prognostic value of aberrant CXCL12 DNA methylation with respect to PD-L1 expression in primary PCa. RESULTS: CXCL12 methylation showed a consistent significant correlation with Gleason grading groups in both cohorts (p < 0.001 for training and p = 0.034 for testing cohort). Short BCR-free survival was significantly associated with aberrant CXCL12 methylation in both cohorts and served as an independent prognostic factor in the testing cohort (hazard ratio = 1.92 [95%CI: 1.12-3.27], p = 0.049). Concomitant aberrant CXCL12 methylation and high PD-L1 expression was significantly associated with shorter BCR-free survival (p = 0.005). In comparative analysis, the CXCL12 methylation assay was able to provide approximately equivalent results in biopsy and prostatectomy specimens. MATERIALS AND METHODS: CXCL12 methylation was determined by means of a methylation specific quantitative PCR analysis in a radical prostatectomy patient cohort (n = 247, training cohort). Data published by The Cancer Genome Atlas served as a testing cohort (n = 498). CXCL12 methylation results were correlated to clinicopathological parameters including biochemical recurrence (BCR)-free survival. CONCLUSIONS: CXCL12 methylation is a powerful prognostic biomarker for BCR in PCa patients after radical prostatectomy. Further studies need to ascertain if CXCL12 methylation may aid in planning active surveillance strategies. |
DOI | 10.18632/oncotarget.10786 |
Alternate Journal | Oncotarget |
PubMed ID | 27462860 |
PubMed Central ID | PMC5288188 |