NLRP2/CASP10-associated signature acts as prognostic biomarker and therapeutic target by regulating anti-tumor immunity and malignant phenotypes in invasive breast carcinoma

The functional interplay between inflammasome components and apoptotic regulators in breast invasive carcinoma (BRCA) remains poorly defined. Here, we investigated the role of the nucleotide-binding leucine-rich repeat family pyrin domain containing 2/caspase−10 (NLRP2/CASP10)-associated signature in BRCA by integrating multi-omics analysis with experimental validation. We analyzed the expression and effects of NLRP2 and CASP10 in patients with BRCA by performing bioinformatic analysis and in vitro experimental validation. We found that in BRCA tissues, high NLRP2 expression was significantly associated with prolonged overall survival, whereas low CASP10 expression was significantly associated with shorter disease-free survival. Both genes were positively correlated with tumor-infiltrating immune cell abundance. Expression of both genes was upregulated in patients who responded to anti-programmed cell death protein 1 / cytotoxic T-lymphocyte-associated protein 4 (anti-PD-1/CTLA-4) immunotherapy. In silico drug prediction analysis and in vitro functional assays revealed that AZ191 (DYRK1B inhibitor) and AZD1332 suppressed proliferation, migration, and invasion of MDA-MB-231 cells and upregulated NLRP2 and CASP10 protein expression. Cells overexpressing these genes exhibited tumor-suppressive phenotypes. Collectively, this study reveals that the NLRP2/CASP10-associated signature is a novel co-regulatory module, prognostic biomarker, mediator of an immune-permissive tumor microenvironment, and promising therapeutic target for BRCA.