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

Frontiers in Genetics

Yiya Zhang¹  Xiaofang Wang²  Zhangya Pu²  Yun Zhong²  Yuanyuan Zhu³  Fang Peng³ 

[1] Department of Dermatology, Xiangya Hospital, Changsha, China;Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China;NHC Key Laboratory of Cancer Proteomics, Xiangya Hospital, Central South University, Changsha, China;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China;

关键词: hepatocellular carcinoma;    competing endogenous RNA network;    immune infiltration;    prognostic prediction model;    biomarkers;   

DOI  :  10.3389/fgene.2021.591623

来源: DOAJ

【 摘 要 】

BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Recently, competing endogenous RNAs (ceRNA) have revealed a significant role in the progression of HCC. Herein, we aimed to construct a ceRNA network to identify potential biomarkers and illustrate its correlation with immune infiltration in HCC.MethodsRNA sequencing data and clinical traits of HCC patients were downloaded from TCGA. The limma R package was used to identify differentially expressed (DE) RNAs. The predicted prognostic model was established using univariate and multivariate Cox regression. A K-M curve, TISIDB and GEPIA website were utilized for survival analysis. Functional annotation was determined using Enrichr and Reactome. Protein-to-protein network analysis was implemented using SRTNG and Cytoscape. Hub gene expression was validated by quantitative polymerase chain reaction, Oncomine and the Hunan Protein Atlas database. Immune infiltration was analyzed by TIMMER, and Drugbank was exploited to identify bioactive compounds.ResultsThe predicted model that was established revealed significant efficacy with 3- and 5-years of the area under ROC at 0.804 and 0.744, respectively. Eleven DEmiRNAs were screened out by a K-M survival analysis. Then, we constructed a ceRNA network, including 56 DElncRNAs, 6 DEmiRNAs, and 28 DEmRNAs. The 28 DEmRNAs were enriched in cancer-related pathways, for example, the TNF signaling pathway. Moreover, six hub genes, CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1, were all overexpressed in HCC tissues and independently correlated with survival rate. Furthermore, expression of hub genes was related to immune cell infiltration in HCC, including B cells, CD8+ T cells, CD4+ T cells, monocytes, macrophages, neutrophils, and dendritic cells.ConclusionThe findings from this study demonstrate that CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1 are closely associated with prognosis and immune infiltration, representing potential therapeutic targets or prognostic biomarkers in HCC.

【 授权许可】

Unknown