Elucidating hepatocellular carcinoma progression: a novel prognostic miRNA-mRNA network and signature analysis

Sci Rep. 2024 Feb 29;14(1):5042. doi: 10.1038/s41598-024-55806-y.

Abstract

There is increasing evidence that miRNAs play an important role in the prognosis of HCC. There is currently a lack of acknowledged models that accurately predict patient prognosis. The aim of this study is to create a miRNA-based model to precisely forecast a patient's prognosis and a miRNA-mRNA network to investigate the function of a targeted mRNA. TCGA miRNA dataset and survival data of HCC patients were downloaded for differential analysis. The outcomes of variance analysis were subjected to univariate and multivariate Cox regression analyses and LASSO analysis. We constructed and visualized prognosis-related models and subsequently used violin plots to probe the function of miRNAs in tumor cells. We predicted the target mRNAs added those to the String database, built PPI protein interaction networks, and screened those mRNA using Cytoscape. The hub mRNA was subjected to GO and KEGG analysis to determine its biological role. Six of them were associated with prognosis: hsa-miR-139-3p, hsa-miR-139-5p, hsa-miR-101-3p, hsa-miR-30d-5p, hsa-miR-5003-3p, and hsa-miR-6844. The prognostic model was highly predictive and consistently performs, with the C index exceeding 0.7 after 1, 3, and 5 years. The model estimated significant differences in the Kaplan-Meier plotter and the model could predict patient prognosis independently of clinical indicators. A relatively stable miRNA prognostic model for HCC patients was constructed, and the model was highly accurate in predicting patients with good stability over 5 years. The miRNA-mRNA network was constructed to explore the function of mRNA.

Keywords: Hepatocellular carcinoma; Prognosis; miRNA; miRNA–mRNA network.

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Gene Regulatory Networks
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • RNA, Messenger
  • MicroRNAs
  • MIRN139 microRNA, human