Integrated Analysis of lncRNA-Mediated ceRNA Network Reveals a Prognostic Signature for Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common types of malignancy and is associated with high mortality. Prior research suggests that long non-coding RNAs (lncRNAs) play a crucial role in the development of HCC. Therefore, it is necessary to identify lncRNA-associated therapeutic biomarkers to improve the accuracy of HCC prognosis. Transcriptomic data of HCC obtained from The Cancer Genome Atlas (TCGA) database were used in the present study. Differentially expressed RNAs (DERNAs), including 74 lncRNAs, 16 miRNAs, and 35 mRNAs, were identified using bioinformatics analysis. The DERNAs were subsequently used to reconstruct a competing endogenous RNA (ceRNA) network. A lncRNA signature was revealed using Cox regression analysis, including LINC00200, MIR137HG, LINC00462, AP002478.1, and HTR2A-AS1. Kaplan-Meier plot demonstrated that the lncRNA signature is highly accurate in discriminating high- and low-risk patients (P < 0.05). The area under curve (AUC) value exceeded 0.7 in both training and validation cohort, suggesting a high prognostic potential of the signature. Furthermore, multivariate Cox regression analysis indicated that both the TNM stage and the lncRNA signature could serve as independent prognostic factors for HCC (P < 0.05). Then, a nomogram comprising the TNM stage and the lncRNA signature was determined to raise the accuracy in predicting the survival of HCC patients. In the present study, we have introduced a ceRNA network that could contribute to provide a new insight into the identification of potential regulation mechanisms for the development of HCC. The five-lncRNA signature could serve as a reliable biosignature for HCC prognosis, while the nomogram possesses strong potential in clinical applications.

Tumor Mutation Burden-Associated LINC00638/miR-4732-3p/ULBP1 Axis Promotes Immune Escape via PD-L1 in Hepatocellular Carcinoma

“…Recent studies set up several prognostic risk models with lncRNAs aimed at predicting the prognosis of patients with HCC via bioinformatics analysis ( 17 , 18 , 41 ). These papers demonstrated the potential clinical value of lncRNAs for predicting HCC patients’ OS.…”

“…The ceRNA network of HOXD-AS1/miR-130a-3p/SOX4 as well as CASC2/miR-367/FBXW7 may play a prometastatic role in HCC ( 15 , 16 ). Moreover, several ceRNA networks have been screened as prognostic signatures for HCC, but further experiments to validate these networks are needed in these studies ( 17 , 18 ). Most importantly, few studies have reported the relationship among the ceRNA network, TMB and immune infiltration in HCC.…”

Identification of Gefitinib Resistance-Related lncRNA-miRNA-mRNA Regulatory Networks and Corresponding Prognostic Signature in Patients with Lung Adenocarcinoma

“… 31 A previous lncRNA signature containing MIR137HG was also reported to be a reliable prognostic model for HCC patients. 32 ZNF295-AS1 was also reported to be highly expressed in human epithelial ovarian cancer via microarrays and RT-qPCR. 33 To date, few studies have investigated the correlation of these lncRNAs with gefitinib resistance.…”

Construction of novel lncRNA-miRNA-mRNA ceRNA networks associated with prognosis of hepatitis C virus related hepatocellular carcinoma

“…Notably, a large number of previous studies have explored the lncRNA/miRNA/mRNA ceRNA network in HCC [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. In contrast to these studies, the present study is the first to investigate the lncRNA/miRNA/mRNA ceRNA network in HCV-related HCC, and the network was associated with patient prognosis.…”