A novel epithelial-mesenchymal transition gene signature for the immune status and prognosis of hepatocellular carcinoma

Hepatol Int. 2022 Aug;16(4):906-917. doi: 10.1007/s12072-022-10354-3. Epub 2022 Jun 14.

Abstract

Background: This study clarified whether EMT-related genes can predict immunotherapy efficacy and overall survival in patients with HCC.

Methods: The RNA-sequencing profiles and patient information of 370 samples were derived from the Cancer Genome Atlas (TCGA) dataset, and EMT-related genes were obtained from the Molecular Signatures database. The signature model was constructed using the least absolute shrinkage and selection operator Cox regression analysis in TCGA cohort. Validation data were obtained from the International Cancer Genome Consortium (ICGC) dataset of patients with HCC. Kaplan-Meier analysis and multivariate Cox analyses were employed to estimate the prognostic value. Immune status and tumor microenvironment were estimated using a single-sample gene set enrichment analysis (ssGSEA). The expression of prognostic genes was verified using qRT-PCR analysis of HCC cell lines.

Results: A signature model was constructed using EMT-related genes to determine HCC prognosis, based on which patients were divided into high-risk and low-risk groups. The risk score, as an independent factor, was related to tumor stage, grade, and immune cells infiltration. The results indicated that the most prognostic genes were highly expressed in the HCC cell lines, but GADD45B was down-regulated. Enrichment analysis suggested that immunoglobulin receptor binding and material metabolism were essential in the prognostic signature.

Conclusion: Our novel prognostic signature model has a vital impact on immune status and prognosis, significantly helping the decision-making related to the diagnosis and treatment of patients with HCC.

Keywords: Bioinformatics; Biomarker; Decision-making; Drug sensitivity; Epithelial–mesenchymal transition; Hepatocellular carcinoma; Immune microenvironment; Model; Overall survival; Prognosis.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / pathology
  • Prognosis
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers, Tumor