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