Development of a novel prognostic signature derived from enhancer RNA‐regulated genes in head neck squamous cell carcinoma

Abstract Background Enhancer RNAs (eRNAs) are increasingly recognized as prognostic biomarkers—across human cancers. Here, we sought to develop a novel eRNA‐regulated genes (ERGs)‐derived prognostic signature for head neck squamous cell carcinoma (HNSCC). Methods Candidate ERGs were identified via co‐expression between individual survival‐related eRNAs and their putative targets by Spearman's correlation analyses. The ERG signature was developed by univariate Cox regression, Kaplan–Meier survival analysis and maximum AUC in 1000 iterations of LASSO‐penalized multivariate Cox regression. An ERG nomogram incorporating ERG signature and selected clinicopathological parameters were constructed by multivariate Cox regression. Biological roles of eRNA of interest were further explored in vitro. Results The ERG signature successfully stratified patients into subgroups with distinct survival in multiple cohorts. An ERG nomogram was developed with satisfactory performance in prognostication. Inhibition of ENSR00000165816 significantly reduced transcript level of SLC2A9 and impaired cell proliferation and invasion. Conclusion Our results establish ERG signature and nomogram as powerful prognostic predictors for HNSCC.