Identification and Validation of an Immune-Related eRNA Prognostic Signature for Hepatocellular Carcinoma

Abstract

BackgroundEnhancer RNAs (eRNAs) are intergenic long non-coding RNAs (lncRNAs) that participate in the progression of malignancies by targeting tumor-related genes and immune checkpoints. However, the potential role of eRNAs in hepatocellular carcinoma (HCC) is unclear. In this study, we aimed to construct an immune-related eRNA prognostic model that could be used to prospectively assess the prognosis of patients with HCC.MethodsGene expression profiles of patients with HCC were downloaded from The Cancer Genome Atlas (TCGA). The eRNAs co-expressed from immune genes were identified as immune-related eRNAs. Cox regression analyses were applied in a training cohort to construct an immune-related eRNA signature (IReRS), that was subsequently used to analyze a testing cohort and combination of the two cohorts. Kaplan-Meier and receiver operating characteristic (ROC) curves were used to validate the predictive effect in the three cohorts. Gene Set Enrishment Analysis (GSEA) computation was used to identify an IReRS-related signaling pathway. A web-based cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) computation was used to evaluate the relationship between the IReRS and infiltrating immune cells.ResultsA total of sixty-four immune-related eRNAs (IReRNAs) was identified in HCC, and 14 IReRNAs were associated with overall survival (OS). Five IReRNAs were used for constructing an immune-related eRNA signature (IReRS), which was shown to correlate with poor survival and to be an independent prognostic biomarker for HCC. The GSEA results showed that the IReRS was correlated to cancer-related and immune-related pathways. Moreover, we found that IReRS was correlated to infiltrating immune cells, including CD8+ T cells and M0 macrophages. Finally, differential expressions of the five risk IReRNAs in tumor tissues vs. adjacent normal tissues and their prognostic values were verified, in which the AL445524.1 may function as an oncogene that affects prognosis partly by regulating CD4-CLTA4 related genes.ConclusionOur results suggest that the IReRS could serve as a biomarker for predicting prognosis in patients with HCC. Additionally, it may be correlated to the tumor immune microenvironment and could also be used as a biomarker in immunotherapy for HCC.

Noncoding RNA-mediated macrophage and cancer cell crosstalk in hepatocellular carcinoma

“…Five IReRNAs (AC073257.2, AL445524.1, FAM120AOS, LINC00513, and STK3) were identified as an IReRNA signature (IReRS), and they are positively correlated with poor survival but inversely correlated with CD8 + T cells and M0 macrophage infiltration in HCC, especially AL445524.1. 239 These data indicate that these eRNAs may play important roles in HCC immunity mediated by T cells and TAMs.…”

Construction of a Novel LncRNA Signature Related to Genomic Instability to Predict the Prognosis and Immune Activity of Patients With Hepatocellular Carcinoma

“…The second was the 12-lncRNA model constructed by Li ( 42 ) (LINC01018, FAM230B, RP11‐290F5.1, APCDD1L‐AS1, FAM99A, LINC01370, AC002116.8, GRM8, RP11‐30J20.1, RP11‐136K7.2, WDR86AS1, and LINC00671). The last was an immune-related LncRNA model created by Cai ( 43 ) (FAM120AOS, AL445524.1, AC073257.2, LINC00513, and STK3). The results showed that the AUC values of the ROC of our signature for the 1-, 2-, and 3-year OS were 0.710, 0.653, and 0.634, respectively, which were significantly higher than those of the other three models ( Figures 6C–E ).…”

A novel immune-related eRNAs prognostic signature to predict the immunotherapy response for thyroid carcinoma

“…EN1 is highly expressed in breast cancer (BRAC), and ESR1 can increase eRNA transcription in BRAC 36 . TAOK1 is associated with overall survival in clear cell renal cell carcinoma 22,37 . SCRIB was differentially expressed among lung adenocarcinoma patients 38 .…”