Yue Chaosen, Ren Yaoyao, Ge Hua, Liang Chaojie, Xu Yingchen, Li Guangming, Wu Jixiang
Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China,
Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China.
Onco Targets Ther. 2019 Jan 14;12:561-576. doi: 10.2147/OTT.S188913. eCollection 2019.
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.
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.
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 (, , , , , , , , , , and ) and two downregulated genes ( and ) whose expression might be regulated by eight DEMs and 61 DELs. Kaplan-Meier curve analysis showed that nine DELs (AL163952.1, AL359878.1, AP002478.1, C2orf48, C10orf91, CLLU1, CLRN1-AS1, ERVMER61-1, and WARS2-IT1) in the ceRNA regulatory network were significantly associated with HCC-patient prognoses.
This study identified potential prognostic genes and constructed an lncRNA- miRNA-mRNA ceRNA regulatory network of HCC, which not only has important clinical significance for early diagnoses but also provides effective targets for HCC treatments and could provide new insights for HCC-interventional strategies.
肝细胞癌（HCC）是一种极为常见的恶性肿瘤，在全球范围内普遍存在。本研究的目的是识别潜在的预后基因，并构建一个竞争性内源性RNA（ceRNA）调控网络，以探索HCC发生发展的潜在机制。
利用R软件，基于GSE14520、GSE17548、GSE19665、GSE29721、GSE60502以及癌症基因组图谱（Cancer Genome Atlas）数据库，对HCC中的潜在预后基因进行综合分析。进行基因本体（Gene Ontology）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes）通路富集分析，以探索潜在预后基因的分子机制。基于癌症基因组图谱数据库筛选差异表达的微小RNA（DEM）和长链非编码RNA（DEL）。根据来自miRcode、TargetScan、miRTarBase和miRDB数据库的相互作用信息构建lncRNA-miRNA-mRNA ceRNA调控网络。
共筛选出152个潜在的预后基因，这些基因在HCC组织中差异表达，且与HCC患者的总生存期显著相关。ceRNA调控网络中有13个关键的潜在预后基因：11个上调基因（……）和2个下调基因（……），其表达可能受8个DEM和61个DEL调控。Kaplan-Meier曲线分析表明，ceRNA调控网络中的9个DEL（AL163952.1、AL359878.1、AP002478.1、C2orf48、C10orf91、CLLU1、CLRN1-AS1、ERVMER61-1和WARS2-IT1）与HCC患者的预后显著相关。
本研究识别了潜在的预后基因，并构建了HCC的lncRNA-miRNA-mRNA ceRNA调控网络，这不仅对早期诊断具有重要临床意义，还为HCC治疗提供了有效靶点，并可为HCC干预策略提供新的见解。
