Immune Analysis and Small Molecule Drug Prediction of Hepatocellular Carcinoma Based on Single Sample Gene Set Enrichment Analysis

Cell Biochem Biophys. 2022 Jun;80(2):427-434. doi: 10.1007/s12013-022-01070-8. Epub 2022 Feb 23.

Abstract

Though patients with hepatocellular carcinoma (HCC) benefit from the treatment of immune checkpoint inhibitor (ICB), it is still of vital significance to develop more effective drugs and predict patients' response to ICB therapy. Herein, we utilized single sample gene set enrichment analysis (ssGSEA) to score the downloaded tumor samples from TCGA-LIHC based on 29 immune gene sets, thus reflecting the immunologic competence of samples. Then samples were classified into high, moderate, and low immunity groups. Additionally, we utilized survival analysis and ESTIMATE score to verify the reliability of the immunity grouping. We then performed differential expression analysis on the samples in these two groups and obtained 716 differentially expressed genes (DEGs). Next, the DEGs mentioned above were subjected to GO and KEGG analyses. The outcomes demonstrated that these DEGs were mostly correlated with the immune-related biological functions. To further verify biological processes in which DEGs might be involved, we constructed a protein-protein interaction network. Afterward, we used MCODE plugin to conduct subnetwork analysis. Thereafter, KEGG enrichment analysis was performed on two genes with the highest score in the subnetwork. The results exhibited that these genes were gathered in pathways such as Th1 and Th2 cell differentiation and NF-κB. Finally, we utilized Connectivity Map to find possible drugs for the treatment of HCC and obtained complex methyl-angolensate. The above results may contribute to distinguishing HCC patients who are eligible for immunotherapy and providing the foundations for the development of therapeutic drugs for HCC.

Keywords: Hepatocellular carcinoma; Immunity grouping; Therapeutic drug; ssGSEA.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / pathology
  • Reproducibility of Results

Substances

  • Biomarkers, Tumor