Construction and clinical evaluation of N6-methyladenosine risk signature of YTHDC2, IGF2BP2, and HNRNPC in head and neck squamous cell carcinoma.

Objectives: This work aimed to construct N6-methyladenosine (m⁶A) regulator-based prognostic signature and evaluate the prognostic value and the intervention on tumor immune microenvironment of this m⁶A risk signature.

Methods: Using transcriptome and clinical data of head and neck squamous cell carcinoma (HNSCC) from The Cancer Genome Atlas (TCGA), we profiled m⁶A regulators and constructed an m⁶A risk signature. The relationship between m⁶A modulation and immune function was studied by differential gene expression, cell type enrichment, and correlation analyses.

Results: Fifteen m⁶A regulators had aberrant expression in HNSCC. A three-gene m⁶A prognostic signature (i.e., YTHDC2, IGF2BP2, and HNRNPC) was constructed and identified as an independent prognostic indicator for HNSCC. The m⁶A 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 m⁶A regulators and tumor immune landscape in HNSCC revealed that the m⁶A 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.