Research Paper Volume 13, Issue 13 pp 17607—17628

Comprehensive analysis of an immune-related ceRNA network in identifying a novel lncRNA signature as a prognostic biomarker for hepatocellular carcinoma

Rui Chen1,2, *, , Yunlong Chen1,2, *, , Wenjie Huang3, , Yingnan Zhao1,2, , Wang Luo1,2, , Jinyu Lin1,2, , Zhuangxiong Wang1,2, , Jian Yang1,2, ,

  • 1 Department of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
  • 2 Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
  • 3 Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, China
* Equal contribution

Received: March 3, 2021       Accepted: June 19, 2021       Published: July 8, 2021
How to Cite

Copyright: © 2021 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The function of competitive endogenous RNA (ceRNA) network in the immune regulation of hepatocellular carcinoma (HCC) is unclear. Our study aimed to construct an immune-related ceRNA network and develop an immune-related long noncoding RNA (lncRNA) signature to assess the prognosis of HCC patients and to optimize the treatment methods. We firstly constructed a ceRNA regulatory network for HCC using differentially expressed lncRNAs, mRNAs and microRNAs (miRNAs) from the Cancer Genome Atlas. A signature was constructed by 11 immune-related prognostic lncRNAs from the ceRNA network. The survival analysis and receiver operating characteristic analysis validated the reliability of the signature. Multivariate Cox regression analysis revealed that the signature could act an independent prognostic indicator. This signature also showed high association with immune cell infiltration and immune check blockades. LINC00491 was identified as the hub lncRNA in the signature. In vitro and in vivo evidence demonstrated that silencing of LINC00491 significantly inhibited HCC growth. Finally, 59 lncRNAs, 21 miRNAs, and 26 mRNAs were obtained to build the immune-related ceRNA network for HCC. In conclusion, our novel immune-related lncRNA prognostic signature and the immune-related ceRNA network might provide in-depth insights into tumor-immune interaction of HCC and promote better individual treatment strategies in HCC patients.


HCC: Hepatocellular carcinoma; lncRNA: long noncoding RNA; miRNA: microRNA; ceRNA: competitive endogenous RNA; MRE: microRNA response elements; CA: colon adenocarcinoma; DE: differentially expressed; TCGA: the Cancer Genome Atlas; ICB: immune checkpoint blockade; LASSO: least absolute shrinkage and selection operator; OS: overall survival; ROC: receiver operating characteristic; AUC: area under the curve; GC: germinal center; FC: fold change; FDR: false discovery rate; ImmPort: Immunology Database and Analysis Portal; MSigDB: Molecular Signatures Database; GSEA: gene set enrichment analysis; CCK-8: Cell Counting Kit-8; AFP: alpha fetoprotein; BMI: body mass index; NSCLC: non-small-cell lung cancer.