Cross-talk between disulfidptosis and immune check point genes defines the tumor microenvironment for the prediction of prognosis and immunotherapies in glioblastoma.

Disulfidptosis is a condition where dysregulated NAPDH levels and abnormal accumulation of cystine and other disulfides occur in cells with high SLC7A11 expression under glucose deficiency. This disrupts normal formation of disulfide bonds among cytoskeletal proteins, leading to histone skeleton collapse and triggering cellular apoptosis. However, the correlation between disulfidptosis and immune responses in relation to glioblastoma survival rates and immunotherapy sensitivity remains understudied. Therefore, we utilized The Cancer Genome Atlas and The Chinese Glioma Genome Atlas to identify disulfidptosis-related immune checkpoint genes and established an overall survival (OS) prediction model comprising six genes: CD276, TNFRSF 14, TNFSF14, TNFSF4, CD40, and TNFRSF18, which could also be used for predicting immunotherapy sensitivity. We identified a cohort of glioblastoma patients classified as high-risk, which exhibited an upregulation of angiogenesis, extracellular matrix remodeling, and epithelial-mesenchymal transition as well as an immunosuppressive tumor microenvironment (TME) enriched with tumor associated macrophages, tumor associated neutrophils, CD8 + T-cell exhaustion. Immunohistochemical staining of CD276 in 144 cases further validated its negative correlation with OS in glioma. Disulfidptosis has the potential to induce chronic inflammation and an immunosuppressive TME in glioblastoma.

Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer.

This study aimed to determine the prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer (HER2+ BC). Transcriptome sequencing and clinicopathological data were downloaded from the Cancer Genome Atlas. The 10X single cell sequencing dataset was downloaded from the National Center for Biotechnology Information Gene Expression Omnibus. Exosomes-Related Genes were extracted from the ExoCarta and Gene Set Enrichment Analysis databases. FGF9, SF3B4, and EPCAM were found and deemed the most accurate predictive signatures. Patients with HER2+ BC were subtyped into three groupings by exosome prognostic gene (EPGs). The expression of SF3B4 was positively linked with the infiltration of macrophages, neutrophils, and CD4+ T cells. The expression characteristics of EPGs were associated with the biological process of "response to xenobiotic stimuli." Interactions were relatively high between malignant epithelial cells and fibroblasts, endothelial cells, monocytes, and macrophages. Malignant epithelial cells interact more with fibroblasts and endothelial cells. The migration inhibitory factor pathway was the primary outgoing signaling pattern, while the C-C motif chemokine ligand pathway was the primary incoming signaling pattern for communication between malignant epithelial cells and macrophages. This study described the role of exosome signatures in the prognosis and microenvironment of HER2+ BC and provided a basis for future research.