Comprehensive analysis of potential prognostic genes for the construction of a competing endogenous RNA regulatory network in hepatocellular carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is an extremely common malignant tumor with worldwide prevalence. The aim of this study was to identify potential prognostic genes and construct a competing endogenous RNA (ceRNA) regulatory network to explore the mechanisms underlying the development of HCC. Methods: Integrated analysis was used to identify potential prognostic genes in HCC with R software based on the GSE14520, GSE17548, GSE19665, GSE29721, GSE60502, and the Cancer Genome Atlas databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway-enrichment analyses were performed to explore the molecular mechanisms of potential prognostic genes. Differentially expressed miRNAs (DEMs) and lncRNAs (DELs) were screened based on the Cancer Genome Atlas database. An lncRNA-miRNA-mRNA ceRNA regulatory network was constructed based on information about interactions derived from the miRcode, TargetScan, miRTarBase, and miRDB databases. Results: A total of 152 potential prognostic genes were screened that were differentially expressed in HCC tissue and significantly associated with overall survival of HCC patients. There were 13 key potential prognostic genes in the ceRNA regulatory network: eleven upregulated genes (CCNB1,

The competitive endogenous RNA regulatory network reveals potential prognostic biomarkers for overall survival in hepatocellular carcinoma

“…Several studies have explored the prognostic biomarkers and possible molecular regulatory pathways of HCC based on competitive endogenous regulatory networks, but did not construct corresponding prognostic models for OS of HCC patients . One mRNA‐based prognostic model was built for OS of HCC patients through a single dataset from TCGA, but did not carry out external validation .…”

“…Long noncoding RNAs could indirectly regulate the expression of mRNAs through competitively binding response elements of miRNAs as endogenous molecular sponges . Several studies have explored the molecular biological regulatory mechanisms for prognosis of HCC patients through the ceRNA regulatory network . Lin et al constructed 3 prognostic prediction models by using lncRNAs, miRNAs, and mRNAs, whereas Bai et al constructed an lncRNA prognostic model for OS in HCC patients based on 13 lncRNAs identified by a ceRNA regulatory network.…”

Identification of Prognostic Biomarkers and Correlation with Immune Infiltrates in Hepatocellular Carcinoma Based on a Competing Endogenous RNA Network

“…Currently, the main treatments for HCC include radiofrequency ablation, surgical resection, immunotherapy, and liver implantation, among others. However, the clinical efficacy of treatments for specific patients is not satisfactory due to poor therapeutic targets, tumor immune escape and complications, leading to a low 5-year survival rate [7,14,28]. In past decades, studies focused on immunotherapy for various cancers have obtained meaningful breakthroughs, especially in melanoma, non-small cell lung cancer, and others.…”

“…Tumorigenesis of HCC is correlated with several liver primary diseases, such as viral infections, including Hepatitis B virus (HBV), Hepatitis C virus (HCV), and other kinds of hepatotropic viruses, as well as alcoholic liver diseases, dietary aflatoxin exposure diabetes, and other diseases [5,6]. Despite continuous improvement in the methods of diagnosis and treatment, HCC remains a global clinical challenge due to its poor prognosis and low rate of 5-year survival [7,8]. Therefore, individual strategies based on identifying early potential prognostic biomarkers and novel therapeutic targets are urgently needed.…”

“…In 2011, the competing endogenous RNA (ceRNA) hypothesis was elucidated for the first time by Salmena et al, demonstrating that ncRNAs not only directly take part in the regulation of targeted gene expression but also absorb corresponding miRNAs as natural sponges due to their typically containing more than one miRNA response element (MRE) that competes with mRNA [9]. Recently, increasing evidence indicates that the regulatory network comprised of lncRNA-miRNA-mRNA plays an important role in the physiology and development of various tumors, including HCC, gallbladder cancer, gastric cancer, and others [3,4,7]. Zhang et al indicated that lncRNA-correlated ceRNA networks are involved in diverse biological cancer pathways in glioblastoma [10].…”