A Novel Defined Necroptosis-Related Genes Prognostic Signature for Predicting Prognosis and Treatment of Osteosarcoma

Biochem Genet. 2024 Apr;62(2):831-852. doi: 10.1007/s10528-023-10446-1. Epub 2023 Jul 17.

Abstract

Osteosarcoma (OS) is a frequent primary malignant bone tumor, with a poor prognosis. Necroptosis is strongly correlated with OS and may be an influential target for treating OS. This study's objective was to establish a necroptosis-related gene (NRG) prognostic signature that could predict OS prognosis and guide OS treatment. First, we identified 20 NRGs associated with OS survival based on the TARGET database. We then derived a 7 NRG prognostic signature. Our findings revealed that the 7 NRG prognostic signature performed well in predicting the survival of OS patients. We next analyzed differences in immunological status and immune cell infiltration. In addition, we examined the relationship between chemo/immunotherapeutic response and the 7-NRG prognostic signature. In addition, to probe the mechanisms underlying the NRG prognostic signature, we performed functional enrichment assays including GO and KEGG. Finally, CHMP4C was selected for functional experiments. Silencing CHMP4C prevented OS cells from proliferating, migrating, and invading. This 7-NRG prognostic signature seems to be an excellent predictor that can provide a fresh direction for OS treatment.

Keywords: Immune; Necroptosis-related genes; Osteosarcoma; Prognostic signature.

MeSH terms

  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / therapy
  • Humans
  • Necroptosis / genetics
  • Osteosarcoma* / genetics
  • Osteosarcoma* / therapy
  • Prognosis