Molecular subtyping and immune score system by a novel pyroptosis-based gene signature precisely predict immune infiltrating, survival and response to immune-checkpoint blockade in breast cancer

Abstract

Breast cancer is one of the most prevalent and lethal types of cancer affecting women globally. Pyroptosis is a recently elucidated form of inflammatory cell death mediated by the gasdermin family and is considered to be associated with the tumor immune microenvironment. However, the impact of pyroptosis on breast cancer patients remains unclear. In this study, we identified 31 Pyroptosis-Related-Genes (PRGs) and investigated their association with patient survival using data from the TCGA database. We then established a gene signature comprising 6 PRGs that were significantly correlated with prognosis, and used these genes to classify breast cancer into 2 molecular subtypes. We investigated the characteristics of these two subtypes and found that our molecular subtyping accurately separated the samples into two groups with distinct immune infiltration and prognosis. Patients with higher expression of these genes had significantly greater immune infiltrating, T cell signaling, and better prognosis. Moreover, we developed an immune score system based on these 6 genes that accurately predicted the immune infiltrating of patients and their response to immune-checkpoint blockade, which was difficult to achieve with previous models. Additionally, through single-cell analyses, we found that patients with higher immune scores had stronger cytotoxic immune cells. In summary, our study identified a novel gene set and developed an immune scoring system based on this gene set that can precisely predict the immune microenvironment and responses to immunotherapy of breast cancer (BRCA) patients, which could be useful in clinical trials.