Identification of Genes Associated with Prognosis and Immunotherapy Prediction in Triple-Negative Breast Cancer via M1/M2 Macrophage Ratio.

ABSTRACT

Background and Objectives: Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, accounts for ap-proximately 10-15% of all breast cancer cases. Currently, there is no effective therapeutic target for TNBC. Tu-mor-associated macrophages (TAMs), which can be phenotypically classified into M1 and M2 subtypes, have been shown to influence the prognosis of various cancers, including ovarian cancer. This study aimed to investigate the role of M1/M2 macrophages in the TNBC tumor microenvironment (TME), with a focus on identifying prognostic genes and predicting immunotherapy response. Materials and Methods: The study employed the CIBERSORT algorithm to analyze immune cell expression in the TME. Genes associated with the M1/M2 macrophage ratio were identified using Pearson correlation analysis and used to classify patients into dis-tinct clusters. Dimensionality reduction techniques, including univariate Cox regression and Lasso, were applied to these genes. The expression of prognostic genes was validated through immunohistochemistry. Results: The study found a high prevalence of TAMs in the TME. Among the patient clusters, 109 differentially expressed genes (DEGs) were identified. Three significant DEGs (LAMP3, GZMB, and CXCL13) were used to construct the riskScores. The riskScore model effectively stratified patients based on mortality risk. Gene Set Enrichment Analysis (GSEA) associated the riskScore with several significant pathways, including mismatch repair, JAK/STAT3 signaling, VEGF signaling, antigen processing presentation, ERBB signaling, and P53 signaling. The study also predicted patient sensitivity to im-munotherapy using the riskScores. The expression of the three significant DEGs was validated through immunohisto-chemistry. Conclusions: The study concluded that the riskScore model, based on the M1/M2 macrophage ratio, is a valid prognostic tool for TNBC. The findings underscore the importance of the TME in TNBC progression and prognosis and highlight the po-tential of the riskScore model in predicting immunotherapy response in TNBC patients.