Paraptosis‐related genes regulate tumor immune microenvironment and predict prognosis in breast cancer

Paraptosis is a non-apoptotic form of programmed cell death, distinct from classical apoptosis in morphology and mechanism. It has been implicated in tumor resistance and immune microenvironment remodeling, but its role in breast cancer (BC) remains unclear. We classified patients into two subtypes based on the expression of paraptosis-related genes. Then, we systematically analyzed the prognosis and tumor microenvironment (TME) associated with these subtypes. In addition, we developed a risk score, named the paraptosis-related risk score (PRRS). We comprehensively analyzed the correlation of paraptosis with BC prognosis, TME, immune score, and drug sensitivity. Then, we performed in vitro experiments to verify the effect of PI4KB on BC. The PRRS can effectively predict the prognosis and immunity of BC. Low PRRS was associated with a favorable prognosis, characterized by reduced tumor purity and enhanced immune cell infiltration. In addition, PRRS can help identify patients who are suitable for specific drug therapies. Finally, we found that PI4KB was highly expressed in BC. Knockdown of PI4KB expression significantly suppressed BC cell proliferation and migration. Our study establishes a robust framework for BC subtype classification and prognostic prediction, providing novel guidance for personalized therapeutic strategies.