The expression and methylation of genes is associated with the prognosis of head and neck squamous cell carcinoma.

The gene family, comprising , , and , is critical in organogenesis and has been evolutionary conserved in animals. genes are associated with the advanced progression and poor prognosis of multiple cancers. However, the relationship between the genes and head and neck squamous cell carcinoma (HNSC) has not been reported. We used data from The Cancer Genome Atlas (TCGA) to analyze the association between mRNA expression and clinicopathological parameters of patients with HNSC. The prognostic value of genes was evaluated using the Kaplan-Meier plotter. Multivariate Cox analysis was used to screen out prognosis-associated genes to identify better prognostic indicators. The potential roles of and in HNSC prognosis were investigated using the protein-protein interaction (PPI) network, Gene Ontology (GO) analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The correlation between and expression or methylation and immune cell infiltration was evaluated using the tumor-immune system interaction database (TISIDB). MethSurv was used to identify DNA methylation and its effect on HNSC prognosis. genes expression was correlated with different cancers. and expression was lower in the patients with HNSC. In HNSC, expression was significantly related to the clinical stage, histologic grade, and N stage, while expression was only significantly related to the histologic grade. The high expression of was significantly related to the histologic grade, T stage, and N stage. Survival analysis revealed that genes had prognostic value in HNSC, which was supported by multivariate Cox analysis. PPI network and enrichment analysis showed that the genes interacting with and belonged predominantly to signaling pathways associated with DNA binding and transcription. Of the CpG DNA methylation sites in and , 28 and 22 were related to the prognosis of HNSC, respectively. Additionally, and expression and methylation was associated with tumor-infiltrating lymphocytes (TILs). The genes were differentially expressed in patients with HNSC, highlighting their essential role in DNA methylation and tumor-infiltrating immune cell regulation, as well as overall prognostic value in HNSC.