The DNA methylation landscape of PD-1 (PDCD1) and adjacent lncRNA AC131097.3 in head and neck squamous cell carcinoma.

Aims: PD-1 expression is associated with DNA methylation in head and neck squamous cell carcinomas (HNSCCs). We performed methylation analysis at single CpG site resolution in order to understand epigenetic regulation. Materials and methods: CpG methylation analysis of PD-1 and long non-coding RNA (lncRNA) AC131097.3 was performed in n = 528 HNSCCs and n = 50 normal adjacent tissues provided by The Cancer Genome Atlas and in isolated leukocytes. Results: PD-1 mRNA and AC131097.3 lncRNA expression correlated inversely with promoter and positively with gene body CpG methylation. PD-1 and AC131097.3 are co-expressed. Methylation was sequence-contextually associated with human papillomavirus prognosis, mutational load, and immune infiltrates. Conclusions: The significance of PD-1 and AC131097.3 methylation is highly sequence-contextual. AC131097.3 might play a role in HNSCC.