A comprehensive analysis based on classification of immunogenic cell death reveals immunologic and prognostic characteristics of breast cancer

Abstract

Abstract Background: Breast cancer (BC) is a main cause of cancer-related mortality in women globally. The immune system plays a vital role in various processes of cancer development and therapy. Neoplastic cells are constantly interacting with and shaping the tumour microenvironment (TME) which in turn influences the cancer development. Immunogenic cell death (ICD) is sufficient to activate an adaptive immune response and contribute to immunotherapy via release of danger signals or damage associated molecular patterns. Method: The Cancer Genome Atlas database and the Gene Expression Omnibus dataset were used to collect 1139 samples, which were then categorized using R software packages. The ICD-related genes were classified into two clusters according to their expression level. The relationships between the different subgroups and clinical pathological characteristics, immune infiltration characteristics, mutation status of the TME and ICD level were investigated. Furthermore, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses used to build an immunological prognostic model was developed to estimate patient survival probability and effect of immunotherapy. Results: We enrolled 1139 patients for analysis and divided the ICD-related genes into two groups based on the expression level. 22 types of tumour infiltrating immune cells in primary BC were quantified by estimating relative subsets of RNA transcripts (CIBERSORT). The results of univariate Cox regression revealed that 9 genes were substantially associated with BC patients' overall survival (OS). OS was significantly shorter in the high-risk group than in the low-risk group, regardless of other characteristics of BC. 7 genes were shown to be closely correlated with the risk score system which was established by the model and utilizing the immune score model may predict the prognosis and immunotherapy effect in patients with BC. Conclusion: The classification system of BC based on ICD signatures is efficient to predict the prognosis of BC patients as well as the effect of immunotherapy.