A novel prognostic signature and therapy guidance for hepatocellular carcinoma based on STEAP family

BMC Med Genomics. 2024 Jan 8;17(1):16. doi: 10.1186/s12920-023-01789-0.

Abstract

Background: The six-transmembrane epithelial antigen of prostate (STEAP) family members are known to be involved in various tumor-related biological processes and showed its huge potential role in tumor immunotherapy.

Methods: Biological differences were investigated through Gene set enrichment analysis (GSEA) and tumor microenvironment analysis by CIBERSORT. Tumor mutation burden (TMB), immunotherapy response and chemotherapeutic drugs sensitivity were estimated in R.

Results: We established a prognostic signature with the formula: risk score = STEAP1 × 0.3994 + STEAP4 × (- 0.7596), which had a favorable concordance with the prediction. The high-risk group were enriched in cell cycle and RNA and protein synthesis related pathways, while the low-risk group were enriched in complement and metabolic related pathways. And the risk score was significantly correlated with immune cell infiltration. Most notably, the patients in the low-risk group were characterized with increased TMB and decreased tumor immune dysfunction and exclusion (TIDE) score, indicating that these patients showed better immune checkpoint blockade response. Meanwhile, we found the patients with high-risk were more sensitive to some drugs related to cell cycle and apoptosis.

Conclusions: The novel signature based on STEAPs may be effective indicators for predicting prognosis, and provides corresponding clinical treatment recommendations for HCC patients based on this classification.

Keywords: Drug sensitivity; Hepatocellular carcinoma; Immunotherapy; Prognosis signature; STEAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / therapy
  • Humans
  • Immunotherapy
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / therapy
  • Male
  • Oxidoreductases
  • Prognosis
  • Prostate
  • Tumor Microenvironment

Substances

  • STEAP1 protein, human
  • Antigens, Neoplasm
  • Oxidoreductases