Pyroptosis-related molecular classification and immune microenvironment infiltration in breast cancer: A novel therapeutic target

The underlying role of pyroptosis in breast cancer (BC) remains unknown. Herein, we investigated the correlations of 33 pyroptosis-related genes (PRGs) with immune checkpoints and immune cell infiltrations in BC patients based on The Cancer Genome Atlas cohort (n = 996) and Gene Expression Omnibus cohort (n = 3,262). Enrichment analysis revealed that these PRGs mainly functioned in pyroptosis, inflammasomes and regulation of autophagy pathway. Four prognostic independent PRGs (CASP9, TIRAP, GSDMC and IL18) were identified. Then, cluster 1/2 was recognized using consensus clustering for these four PRGs. Patients from cluster 1 had a favourable prognosis and diverse immune cell infiltrations. A nomogram was developed based on age, TNM stage, tumour subtype and pyroptosis score. Patients with the high-risk group exhibited worse 5-year OS, and the result was consistent in the external cohort. Additionally, high-risk group patients were associated with downregulated immune checkpoint expression. Further analysis suggested that the high-risk group patients were associated with a higher IC50 of paclitaxel, doxorubicin, cisplatin, methotrexate and vinorelbine. In summarizing, the pyroptosis score-based nomogram might serve as an independent prognostic predictor and could guide medication for chemotherapy. Additionally, it may bring novel insight into the regulation of tumour immune microenvironment in BC and help to achieve precision immunotherapy.