Promoter methylation of the immune checkpoint receptor PD-1 (PDCD1) is an independent prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy

Abstract

Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 (PDCD1) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn.In the TCGA cohort, the PD-1 promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs. 38.2%, p < 0.001) and PD-1 methylation (mPD-1) inversely correlated with PD-1 mRNA expression in PCa (Spearman's r D ¡0.415, p < 0.001). In both cohorts, mPD-1 significantly correlated with preoperative prostate specific antigen (PSA). In univariate Cox Proportional Hazard analysis, mPD-1 served as a significant prognostic factor for biochemical recurrence ( PD-1 promoter methylation analyses could thus potentially aid the identification of patients which might benefit from adjuvant treatment after radical prostatectomy. Moreover, our data suggest an intrinsic role of PD-1 in PCa carcinogenesis and disease progression, which needs to be addressed in future studies.

The PD-1/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: A multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

“…Mixed findings have been reported regarding the role of PD‐1+ TILs that varied depending on tumor type. Indeed, a favorable role has been revealed for PD‐1+ TILs in ovarian, pancreatic, colorectal cancers, whereas in prostate, renal and lung cancers, and melanoma high PD‐1 expression was associated with worse survival rates . Of note, the prognostic role of this immune marker was tumor compartment‐dependent in our work.…”

Large-scale analysis reveals the specific clinical and immune features of B7-H3 in glioma

“…DNA demethylation is considered to be one of the reasons for some immune checkpoints being up-regulated in tumor sites. 14 Consequently, we explored methylation pattern of B7-H3 in whole grade glioma and found that B7-H3 gene promoter was significantly hypomethylated in glioblastoma in both CGGA and TCGA datasets (Fig. S2).…”

LAG3(LAG-3,CD223) DNA methylation correlates with LAG3 expression by tumor and immune cells, immune cell infiltration, and overall survival in clear cell renal cell carcinoma

“…Shown is chromosome 12, position 6 771 404-6 779 853, including the LAG3 gene, its transcripts and regulatory elements (promoter, promoter flank, and CCCTCbinding factor (CTCF) binding site), and the investigated loci. The LAG3 methylation target sites of the HumanMethylation450 BeadChip beads (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) and qMSP assays (4 and 8) are based on Genome Reference Consortium Human Build 38 patch release 13 (GRCh38.p13). The illustration (modified) was exported from www.ensemble.org (release 98).…”

“…The illustration (modified) was exported from www.ensemble.org (release 98). 50 Beads are numbered as follows: cg26956535 (1), cg22777668 (2), cg16352928 (3), cg02695343 (4), cg10500147 (5), cg17213699 (6), cg19872463 (7), cg04671742 (8), cg01820374 (9), cg19421125 (10), cg10191002 (11), cg20652042 (12), cg06157570 (13), cg14292870 (14), cg11429292 (15), and cg15828668 (16). LAG3, lymphocyte activating 3; qMSP, quantitative methylation-specific PCR.…”