Prognostic and Immune Implications of a Novel Pyroptosis-Related Five-Gene Signature in Breast Cancer

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide, with enormous heterogeneity. Pyroptosis has a significant impact on the development and progression of tumors. Nonetheless, the possible correlation between pyroptosis-related genes (PRGs) and the BC immune microenvironment has yet to be investigated. MATERIALS AND METHODS: In The Cancer Genome Atlas Breast Cancer cohort, 38 PRGs were shown to be significantly different between malignant and non-malignant breast tissues. The 38 PRGs’ consensus clustering grouped 1,089 individuals into two pyroptosis-related (PR) patterns. Using univariate and LASSO-Cox analyses, a PR five-gene predictive signature was constructed based on the differentially expressed genes between two clusters. The tools estimation of stromal and immune cells in malignant tumours using expression data (ESTIMATE), cell type identification by estimating relative subsets Of RNA transcripts (CIBERSORT), and single-sample gene set enrichment analysis (ssGSEA) were used to investigate the BC tumor microenvironment (TME). RESULTS: In TME, the two PR clusters displayed distinct clinicopathological characteristics, survival outcomes, and immunocyte infiltration features. The developed five-signature model (SEMA3B, IGKC, KLRB1, BIRC3, and PSME2) classified BC patients into two risk groups based on the estimated median risk score. Patients in the low-scoring category had a higher chance of survival and more extensive immunocyte infiltration. An external validation set can yield similar results. CONCLUSION: Our data suggest that PRGs have a significant impact on the BC immunological microenvironment. The PR clusters and associated predictive signature stimulate additional research into pyroptosis in order to optimize therapeutic strategies for BC patients and their responses to immune therapy.