Identification of novel enhancer RNA biomarkers and corresponding prognostic signatures of hepatocellular carcinoma

Abstract Background Researchers now pique an interest in pursuing investigations of enhancer RNAs (eRNAs ). Their roles in the tumorigenesis regulatory mechanism of hepatocellular carcinoma (HCC) remain to be elucidated. Further investigation on eRNAs may shed light on putative prognosis biomarkers and therapeutic targets, which may benefit for early diagnosis of HCC. Methods RNA-Seq data and clinical information were obtained from The Cancer Genome Atlas (TCGA). Data were analyzed using R software. Prognosis-related eRNAs were identified, and the target genes of eRNAs were predicted based on the correlation level. We performed enrichment analyses and constructed prognostic model using selected eRNA and target genes, then systematically evaluated prognostic effect. The selected target genes were also analyzed in pan-cancer. Results ERNA expression levels were summarized, and 125 prognosis-related eRNAs were identified. Among them, 43 eRNAs were identified because of having putative downstream target genes. After searching literatures, 15 eRNA and target gene pairs were selected for the association with HCC tumorigenesis process or biological behaviors. We chose AL137803.1 for further investigation. The differentially expressed target genes of AL137803.1 in HCC were determined. We performed enrichment analyses and univariate and multivariate cos regression results revealed C5orf58, NDC1, LINC00501 and G6PD could be prognostic signatures of HCC. The prediction value was validated and pan-cancer analyses also demonstrated multiple function of the key eRNA and its target genes. Conclusion A novel eRNA AL137803.1 may be a potential biomarker of HCC, besides its putative target genes may serve as prognostic signatures.