Table 1. Association of PD-L1 and PD-L2 methylation with mRNA expression and HPV-status.
| Analyte | Median methylation [%] and mRNA expression [normalized counts] | Correlation with PD-1 methylation† | Correlation with PD-1 mRNA expression† | Correlation with PD-L1 mRNA expression† | Correlation with PD-L2 mRNA expression† | Median methylation [%] and mRNA expression [normalized counts] | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Tumor | NAT | p-value‡ | Spearman’s ρ | p-value | Spearman’s ρ | p-value | Spearman’s ρ | p-value | Spearman’s ρ | p-value | HPV-neg. | HPV-pos. | p-value‡ | |
| PD-L1 mRNA | 80.6 | 54.0 | 0.31 | 0.063 | 0.15 | 0.520 | <0.001 | NA | NA | 0.761 | <0.001 | 82.3 | 88.0 | 0.42 |
| PD-L2 mRNA | 98.0 | 47.6 | <0.001 | 0.104 | 0.018 | 0.491 | <0.001 | 0.761 | <0.001 | NA | NA | 115.6 | 67.1 | 0.023 |
| mPD-L1 (cg15837913) | 13.0 | 17.3 | <0.001 | 0.106 | 0.015 | –0.314 | <0.001 | –0.320 | <0.001 | –0.197 | <0.001 | 13.9 | 11.1 | 0.051 |
| mPD-L1 (cg02823866) | 3.10 | 3.31 | 0.026 | –0.053 | 0.22 | –0.077 | 0.078 | –0.133 | 0.002 | –0.107 | 0.014 | 3.20 | 3.35 | 0.23 |
| mPD-L1 (cg14305799) | 1.96 | 1.85 | 0.001 | –0.026 | 0.55 | –0.150 | 0.001 | –0.183 | <0.001 | –0.199 | <0.001 | 1.93 | 2.05 | 0.28 |
| mPD-L1 (cg13474877) | 5.57 | 5.94 | 0.047 | –0.017 | 0.70 | –0.250 | <0.001 | –0.327 | <0.001 | –0.241 | <0.001 | 5.84 | 5.70 | 0.82 |
| mPD-L1 (cg19724470) | 11.4 | 17.0 | <0.001 | 0.120 | 0.006 | –0.240 | <0.001 | –0.444 | <0.001 | –0.322 | <0.001 | 12.6 | 18.0 | 0.011 |
| mPD-L2 (cg14440664) | 55.1 | 80.1 | <0.001 | –0.053 | 0.22 | 0.283 | <0.001 | 0.007 | 0.87 | –0.176 | <0.001 | 53.8 | 82.1 | <0.001 |
| mPD-L2 (cg07211259) | 6.0 | 13.0 | <0.001 | 0.240 | <0.001 | –0.174 | <0.001 | –0.160 | <0.001 | –0.153 | <0.001 | 6.42 | 6.45 | 0.61 |
DNA methylation of the PD-L1 and PD-L2 gene loci and correlation/association with PD-L1 and PD-L2 mRNA expression, PD-1 methylation and PD-1 mRNA expression, and HPV-status. DNA methylation of the PD-L1 and PD-L2 gene loci were determined at five and two positions (Figure 1), respectively, within the promoter regions. Methylation data, mRNA expression data, and HPV status were available for n = 528 tumors and n = 50 NATs (methylation), n = 520 tumors and n = 50 NATs (mRNA), and n = 279 tumors (HPV), respectively. PD-1 methylation data were adopted from Goltz et al. [19] and HPV-status as determined via RNAseq (n = 36 HPV-positive, n = 243 HPV-negative tumors) was extracted from The Cancer Genome Atlas Research Network [3]. ‡Mann-Whitney U test, †Spearman’s correlation; NA: Not Applicable.