Integrative Analysis of N6-Methyladenosine-Related Enhancer RNAs Identifies Distinct Prognosis and Tumor Immune Micro-Environment Patterns in Head and Neck Squamous Cell Carcinoma

Abstract

At present, the prognostic value of N6-methyladenosine (m6A)-related enhancer RNAs (eRNAs) for head and neck squamous cell carcinoma (HNSCC) still remains unclear. Our study aims to explore the prognostic value of m6A-related eRNAs in HNSCC patients and their potential significance in immune infiltration and immunotherapy. We constructed a 5 m6A-related eRNAs risk model from The Cancer Genome Atlas (TCGA) HNSCC dataset, using univariate and multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis. Based on the SRAMP website and in vitro experiments, it was verified that these 5 m6A-related eRNAs had m6A sites, the expression of which was regulated by corresponding m6A regulators. Moreover, we constructed a nomogram base on 5 m6A-related eRNAs and confirmed the consistency and robustness of an internal TCGA testing set. Further analysis found that the risk score was positively associated with low overall survival (OS), tumor cell metastasis, metabolic reprogramming, low immune surveillance, lower expression of immune-related genes, and higher expression of targeted genes. Finally, we verified that silencing MIR4435-2HG inhibited HNSCC cell migration and invasion. This study contributes to the understanding of the characteristics of m6A-related eRNAs in HNSCC and provides a reference for effective immunotherapy and targeted therapy.

Keywords

• head and neck squamous cell carcinoma
• N6-methyladenosine
• enhancer RNA
• immunity