| Gastric cancer (GC) is considered one of the most lethal malignancies worldwide due to poor prognosis. Aberrant
methylation has been demonstrated to be involved in PD-L1 dysregulated expression in human cancers and
possesses a great value as a diagnostic biomarker. Given that, in this study, we investigated the methylation
status of PD-L1 as a promising biomarker in primary gastric tumors and identifed functional CpG loci undergoing aberrant methylation through tumorigenesis of GC. PD-L1 methylation was initially evaluated in-silico
using TCGA-STAD dataset. Pearson’s correlation analysis was further employed to identify the most signifcant functional methylated CpG loci of PD-L1 gene in TCGA-STAD patient cohort. Methylation status and its
correlation with PD-L1 expression were also validated using q-MSP and qRT-PCR in a set of internal samples,
including 25 paired primary gastric tumors and adjacent normal tissues. The obtained results from TCGA-STAD
showed that PD-L1 is signifcantly hypermethylated through gastric tumorigenesis, mostly in two CpG loci
overlapping with cg19724470 and cg15837913 probes. Besides, PD-L1 DNA methylation was negatively
correlated with PD-L1 expression in tumor samples. Furthermore, hypermethylation of cg19724470 and
cg15837913 regions was validated in primary gastric tumors compared to adjacent normal samples. Also, ROC
curve analysis illustrated the high diagnostic value of PD-L1 methylation for early detection of GC (AUC =
0.8110). In conclusion, the fndings of this study suggested that PD-L1 expression is regulated by methylation in
functional CpG loci and its methylation could be considered as a valuable diagnostic target for GC. |