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.

Statistical analysis has shown that the new cases and deaths worldwide for oral cancer ranked 18th and 15th among all malignant tumors in 2018 (Bray et al., 2018). As one of the most common and representative types of oral cancer, oral squamous cell carcinoma (OSCC) has become a growing health concern. The survival outcome of OSCC is remaining poor, and existing reports show that its 5-year survival is about 50% (Zhang et al., 2015). Even in the early stage (cT1-2N0), OSCC patients are prone to occur local-regional recurrence and distant metastasis, which may lead to poor prognosis (Zhan et al., 2018). It has been reported that the 5-year survival rate for early-stage OSCC after surgery is approximately 70% (Ellis et al., 2017;Sowder et al., 2017). To improve patient survival, it is necessary to investigate new noninvasive and easily accessible biomarkers for predicting the prognosis of cT1-2N0 OSCC and guiding their treatment.In 1863, Rudolf Virchow firstly explained the relationship between inflammation and cancer. Over the past few decades, we had an understanding of the inflammatory microenvironment of malignant tissues and utilized the link between cancer and inflammation for tumor prevention and treatment (Balkwill & Mantovani, 2001).

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