CXCL12 promoter methylation and PD-L1 expression as prognostic biomarkers in prostate cancer patients

This is the authors' abstract. We don't add key points for this paper.

// Diane Goltz 1, * , Emily Eva Holmes 1, * , Heidrun Gevensleben 1 , Verena Sailer 2, 3 , Jörn Dietrich 1 , Maria Jung 1 , Magda Röhler 1 , Sebastian Meller 1 , Jörg Ellinger 4 , Glen Kristiansen 1 ,# , Dimo Dietrich 1 ,5 ,# 1 Institute of Pathology, University Hospital Bonn, Bonn, Germany 2 Weill Cornell Medicine of Cornell University, Department of Pathology and Laboratory Medicine, New York, NY, USA 3 Weill Cornell Medicine of Cornell University, Englander Institute for Precision Medicine, New York, NY, USA 4 Department of Urology, University Hospital Bonn, Bonn, Germany 5 Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany * These authors have contributed equally to this work # These authors are joint senior authors on this work Correspondence to: Dimo Dietrich, email: dimo.dietrich@gmail.com Keywords: CXCL12, DNA methylation, prostate cancer, biomarker Received: December 25, 2015      Accepted: June 26, 2016      Published: July 22, 2016 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.