Exploring PANoptosis in breast cancer based on scRNA-seq and bulk-seq

Abstract

Background: PANoptosis, a cell death pathway involving pyroptosis, apoptosis, and necroptosis, is pivotal in the development of malignancy. However, in the field of breast cancer, the interaction between PANoptosis and tumor cells has not been thoroughly explored.

Methods: We downloaded breast cancer data and GSE176078 single-cell sequencing dataset from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases to obtain PANoptosis-associated genes. To construct prognostic models, COX and LASSO regression was used to identify PANoptosis-associated genes with prognostic value. Finally, immune infiltration analysis and differential analysis of biological functions were performed.

Results: Risk grouping was performed according to the prognostic model constructed by COX regression and LASSO regression. The low-risk group showed a better prognosis (P < 0.05) and possessed higher levels of immune infiltration and expression of immune checkpoint-related genes. In addition, the lower the risk score, the higher the degree of microsatellite instability (MSI). Meanwhile, radixin (RDX), the gene with the highest hazard ratio (HR) value among PANoptosis prognosis-related genes, was explicitly expressed in artery Iendothelial cells (ECs) and was widely involved in signaling pathways such as immune response and cell proliferation, possessing rich biological functions.

Conclusion: We demonstrated the potential of PANoptosis-based molecular clustering and prognostic features in predicting the survival of breast cancer patients. Furthermore, this study has led to a deeper understanding of the role of PANoptosis in breast cancer and has the potential to provide new directions for immunotherapy of breast cancer.

Keywords: PANoptosis; ScRNA-seq; breast cancer; immunotherapy; tumor immunity.