A tumor microenvironment-related risk model for predicting the prognosis and tumor immunity of breast cancer patients

Abstract

Background: This study aimed to construct a tumor microenvironment (TME)-related risk model to predict the overall survival (OS) of patients with breast cancer.

Methods: Gene expression data from The Cancer Genome Atlas was used as the training set. Differentially expressed gene analysis, prognosis analysis, weighted gene co-expression network analysis, Least Absolute Shrinkage and Selection Operator regression analysis, and Wald stepwise Cox regression were performed to screen for the TME-related risk model. Three Gene Expression Omnibus databases were used to validate the predictive efficiency of the prognostic model. The TME-risk-related biological function was investigated using the gene set enrichment analysis (GSEA) method. Tumor immune and mutation signatures were analyzed between low- and high-TME-risk groups. The patients' response to chemotherapy and immunotherapy were evaluated by the tumor immune dysfunction and exclusion (TIDE) score and immunophenscore (IPS).

Results: Five TME-related genes were screened for constructing a prognostic signature. Higher TME risk scores were significantly associated with worse clinical outcomes in the training set and the validation set. Correlation and stratification analyses also confirmed the predictive efficiency of the TME risk model in different subtypes and stages of breast cancer. Furthermore, immune checkpoint expression and immune cell infiltration were found to be upregulated in the low-TME-risk group. Biological processes related to immune response functions were proved to be enriched in the low-TME-risk group through GSEA analysis. Tumor mutation analysis and TIDE and IPS analyses showed that the high-TME-risk group had more tumor mutation burden and responded better to immunotherapy.

Conclusion: The novel and robust TME-related risk model had a strong implication for breast cancer patients in OS, immune response, and therapeutic efficiency.

Keywords: breast cancer; prognostic factor; therapeutic efficiency; tumor immunity; tumor microenvironment.