Gene signatures of m5C regulators may predict prognoses of patients with head and neck squamous cell carcinoma.

BACKGROUND

Head and neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy in the world. The 5-methylcytosine (m5C) plays vital roles in pathological conditions, such as cancer.

METHODS

This study investigated The Cancer Genome Atlas (TCGA) database for patients with HNSCC. We characterized the mutations and copy number variations (CNVs) in m5C-regulatory genes, in addition to analyzing their mRNA expressions. Gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) analyses were used to explore relevant functional annotations of m5C-regulatory genes.

RESULTS

Alterations in m5C-regulatory genes were closely associated with patient clinicopathological characteristics. The expression of ten m5C-regulatory genes was significantly correlated with CNV patterns, indicating that m5C-regulatory genes have important regulatory effects. There was increased expression of m5C-regulatory genes, particularly ALYREF and NSUN5, during the tumor, node, and metastasis stages. Cox regression analysis revealed that the expression of DNMT1, TET2, and NSUN6 correlated with HNSCC prognoses. Furthermore, the expression of DNMT1 and ALYREF could effectively predict HNSCC risk in patients. In addition, the high expression levels of ALYREF correlated with mitochondrial function, and the elevated DNMT1 expression was associated with peptide cross-linking and humoral immunity. These results provide promising insight into the roles of m5C genes in tumor energy-metabolism and protein synthesis.

CONCLUSIONS

Collectively, the results indicate that m5C plays critical roles in HNSCC progression, and is also a potential HNSCC prognostic marker.