Abstract

<div>Abstract<p>Enhancer RNAs (eRNA) regulate gene expression and play critical roles in cancer. Using large-scale omics data from The Cancer Genome Atlas (TCGA), we systematically investigated the impact of genetic variants on eRNA expression and identified approximately 1 million eRNA quantitative trait loci (eRNA-QTL) as <i>cis</i>- and <i>trans</i>-acting. Over 16,000 eRNA-QTLs were associated with patient overall survival. Assessing the impact of eRNAs on more than 1,000 imputed anticancer drug responses across approximately 10,000 patients with cancer revealed more than 7 million significant associations. Furthermore, approximately 240,000 significant associations were identified between eRNA expression and immune cell abundance deconvoluted by TIMER, CIBERSORT, ImmuCellAI, and ImmuneCellGSVA. Finally, a user-friendly data portal was generated: Genetic, Pharmacogenomic, and Immune Landscapes of eRNAs (GPIeR; <a href="https://hanlab.tamhsc.edu/GPIeR/" target="_blank">https://hanlab.tamhsc.edu/GPIeR/</a>). GPIeR is a large-scale multidimensional data portal that can be used to explore eRNA-associated genetic variants, drug responses, and immune infiltration, with the purpose of facilitating functional and clinical investigations of eRNAs in cancer.</p>Significance:<p>This study provides insights into the impact of the enhancer RNA (eRNA) landscape on patient outcome, the immune microenvironment, and drug response across cancers and develops a multidimensional data portal to facilitate eRNA research.</p></div>

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