Immune-related microRNA signature for predicting prognosis and the immune microenvironment in hepatocellular carcinoma

Life Sci. 2021 Jan 15:265:118799. doi: 10.1016/j.lfs.2020.118799. Epub 2020 Nov 19.

Abstract

Aims: As vital regulators of post-transcription gene expression, microRNAs are involved in the initiation and progression of hepatocellular carcinoma (HCC), including antitumor immune responses. We aimed to identify an immune-related microRNA signature and explore the influence of this signature on the prognosis and immunity of HCC.

Materials and methods: Differentially expressed immune-related microRNAs were identified between high- and low-immunity groups in the TCGA-HCC dataset. Then, Cox regression models were used to construct an immune-related microRNA signature. We assessed the prognostic value and clinical relevance of this signature. Furthermore, we analyzed the effect of the immune-related microRNA signature on immune cells and immune checkpoints.

Key findings: We screened 41 differentially expressed immune-related microRNAs, of which 7 microRNAs were used to construct the immune signature. Survival analysis showed that high-risk patients had a shorter survival. The immune-related microRNA signature was an independent prognostic marker and was associated with the clinical stage. To understand the functional mechanism of the seven-microRNA signature, we predicted target genes of microRNAs. Enrichment analysis indicated that these target genes participated in immune responses. Moreover, we found that the microRNA signature was related to tumor-infiltrating immune cells. In high-risk patients, there was a higher expression of inhibitory immune checkpoints. On the contrary, the expression of stimulatory immune checkpoints was lower in high-risk patients.

Significance: We successfully identified an immune-related microRNA signature that was strongly correlated with the prognosis and immune microenvironment of HCC. The immune-related microRNAs signature might have important implications for improving the clinical outcomes of HCC patients.

Keywords: Hepatocellular carcinoma; Immune cells; Immune checkpoints; Prognosis; microRNA.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology*
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / immunology*
  • Female
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics
  • Liver Neoplasms / immunology*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Transcriptome
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology*

Substances

  • Biomarkers, Tumor
  • MicroRNAs