Deciphering the prognostic and therapeutic significance of BAG1 and BAG2 for predicting distinct survival outcome and effects on liposarcoma

Sci Rep. 2024 Oct 4;14(1):23084. doi: 10.1038/s41598-024-67659-6.

Abstract

Liposarcoma (LPS) is the second most common kind of soft tissue sarcoma, and a heterogeneous malignant tumor derived from adipose tissue. Up to now, the prognostic value of BAG1 or BAG2 in LPS has not been defined yet. Expression profiling data of LPS patients were collected from TCGA and GEO database. Survival curves were plotted to verify the outcome differences of patients based on BAG1 or BAG2 expression. Univariate and multivariate Cox regression models were used to analyze the prognostic ability of BAG1 or BAG2. Chaperone's regulators BAG1 and BAG2 were identified as prognostic biomarkers for LPS patients, which exhibited distinct expression patterns and survival outcome prediction performances. Patients with high BAG2 expression and/or low BAG1 expression had worse prognosis. Enrichment analysis showed that BAG1 was involved in negative regulation of TGF-β signaling. Low expression of BAG1 was associated with high abundance of regulatory T cells (Tregs). The 2-gene signature model further confirmed the improved risk assessment performance of BAG1 and BAG2: high risk patients displayed poor prognosis. BAG1 and BAG2 are supposed to be potential prognostic biomarkers for LPS and have impacts on liposarcomagenesis and immune infiltration in distinctive manners, which may function as potential therapy targets (BAG1 agonists/BAG2 inhibitors) for LPS.

Keywords: BAG1; BAG2; Gene signature; Immune infiltration; Liposarcoma; Prognostic biomarker.

MeSH terms

  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liposarcoma* / genetics
  • Liposarcoma* / metabolism
  • Liposarcoma* / mortality
  • Liposarcoma* / pathology
  • Male
  • Middle Aged
  • Molecular Chaperones
  • Prognosis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • BCL2-associated athanogene 1 protein
  • DNA-Binding Proteins
  • Biomarkers, Tumor
  • BAG2 protein, human
  • Transcription Factors
  • Molecular Chaperones