Cross-talk between disulfidptosis and immune check point genes defines the tumor microenvironment for the prediction...

Area of Science:

• Cellular biology
• Cancer research
• Immunology

Background:

• Disulfidptosis is a cell death pathway triggered by glucose deficiency, high SLC7A11 expression, and disrupted disulfide bond formation.
• This process leads to cytoskeletal collapse and apoptosis, but its role in glioblastoma immunity is unclear.

Purpose of the Study:

• To investigate the link between disulfidptosis and immune responses in glioblastoma.
• To identify disulfidptosis-related genes for predicting glioblastoma survival and immunotherapy sensitivity.

Main Methods:

• Utilized The Cancer Genome Atlas and The Chinese Glioma Genome Atlas datasets.
• Identified disulfidptosis-related immune checkpoint genes.
• Developed an overall survival (OS) prediction model using six genes: CD276, TNFRSF14, TNFSF14, TNFSF4, CD40, and TNFRSF18.
• Performed immunohistochemical staining for CD276.

Main Results:

• Established a six-gene OS prediction model also predictive of immunotherapy sensitivity.
• Identified a high-risk glioblastoma cohort with upregulated angiogenesis, ECM remodeling, EMT, and an immunosuppressive tumor microenvironment (TME).
• The TME was enriched with immunosuppressive cells like tumor-associated macrophages and neutrophils, and showed CD8+ T-cell exhaustion.
• CD276 expression negatively correlated with OS in glioma patients.

Conclusions:

• Disulfidptosis contributes to an immunosuppressive TME and chronic inflammation in glioblastoma.
• The identified gene signature and CD276 hold potential for predicting glioblastoma prognosis and immunotherapy response.