Abstract
OBJECTIVES: This work aimed to construct N6-methyladenosine (m(6)A) regulator-based prognostic signature and evaluate the prognostic value and the intervention on tumor immune microenvironment of this m(6)A risk signature. METHODS: Using transcriptome and clinical data of head and neck squamous cell carcinoma (HNSCC) from The Cancer Genome Atlas (TCGA), we profiled m(6)A regulators and constructed an m(6)A risk signature. The relationship between m(6)A modulation and immune function was studied by differential gene expression, cell type enrichment, and correlation analyses. RESULTS: Fifteen m(6)A regulators had aberrant expression in HNSCC. A three-gene m(6)A prognostic signature (i.e., YTHDC2, IGF2BP2, and HNRNPC) was constructed and identified as an independent prognostic indicator for HNSCC. The m(6)A regulator signature-based high-risk group revealed pro-tumoral immune microenvironment due to the dysregulation of immune-related gene expression, abnormal enrichment of multiple immunocytes, and production of immunoregulatory factors. CONCLUSIONS: This comprehensive analysis of m(6)A regulators and tumor immune landscape in HNSCC revealed that the m(6)A signature of YTHDC2, IGF2BP2, and HNRNPC could serve as a promising biomarker for monitoring HNSCC development and may be a potential target for tumor therapy in the future.