Triple-negative breast cancer (TNBC) is associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity.There is an urgent need to screen for reliable indices, especially immunotherapy-associated biomarkers that can predict patient outcomes.Pyroptosis, as an inflammation-induced type of programmed cell death, is shown to create a tumor-suppressive environment and improve the chemotherapeutic response in multiple tumors.However, the specific therapeutic effect of pyroptosis in TNBC remains unclear.In this study, we present a consensus clustering by pyroptosis-related signatures of 119 patients with TNBC into two subtypes (clusterA and clusterB) with distinct immunological and prognostic characteristics.
First, clusterB, Candles associated with better outcomes, was characterized by a significantly higher pyroptosis-related signature expression, tumor microenvironment prognostic score, and upregulation of immunotherapy checkpoints.A total of 262 differentially expressed genes between the subtypes were further identified and the Ps-score was built using LASSO and COX regression analyses.The external GEO data set demonstrated that cohorts with low Ps-scores consistently had higher expression of pyroptosis-related signatures, immunocyte infiltration levels, and better prognosis.In addition, external immunotherapy and chemotherapy cohorts validated that patients with lower Ps-scores exhibited significant therapeutic response and clinical benefit.Combined with other clinical characteristics, we successfully constructed a nomogram to effectively predict the survival rate of patients with TNBC.
Finally, using the scRNA-seq data sets, we validated the landscape of cellular subtypes of TNBC and successfully constructed an miRNA-Ps-score gene interaction network.These findings indicated that the systematic assessment of tumor pyroptosis and identification of Ps-scores has potential clinical implications and facilitates tailoring optimal CITRUS SOAP immunotherapeutic strategies for TNBC.