Focal pyroptosis-related genes AIM2 and ZBP1 are prognostic markers for triple-negative breast cancer with brain metastases

BACKGROUND: Extensive research has shown the role of pyroptosis in the occurrence, progression, and prognosis of breast cancer. The study sought to screen important pyroptosis-related genes and their role in the prognosis of triple-negative breast cancer (TNBC) patients with brain metastasis (BM). METHODS: The Gene Expression Omnibus database was used to obtain transcriptome data from primary TNBC and from TNBC BM patients. Differentially expressed genes (DEGs) between the primary tumors and BMs were analyzed, and the expression, prognostic significance, immune infiltration, function, and drug sensitivity of the pyroptosis genes in the DEGs were analyzed. RESULTS: In both data sets, 456 genes differed between primary TNBC and TNBC BM. Absent in melanoma 2 (AIM2) and Z-deoxyribonucleic acid-binding protein 1 (ZBP1) were found to be important pyroptosis genes in DEGs, and significant differences in their expression in primary lesions and BMs were observed. Patients with a high expression of AIM2 had a worse prognosis than low expression, while patients with a high expression of ZBP1 had a better prognosis than low expression. AIM2 and ZBP1 were positively correlated with the infiltration of most immune cells; however, AIM2 was negatively correlated with the infiltration of neural cell adhesion molecule 1 (CD56) bright natural killer cells and central memory cluster of differentiation 8 (CD8) T cells. Increased expression of ZBP1 is negatively correlated with high infiltration levels of central memory CD8 T cells and memory B cells. CONCLUSIONS: Our findings suggest that AIM2 and ZBP1 increase immune cell infiltration and may be potential targets for predicting and treating TNBC BM.