SPIB Modulates Macrophage Polarization and Correlates with Prognosis in Breast Cancer.

Abstract

Breast cancer (BC) is the leading malignancy affecting women globally, characterized by significant heterogeneity. Therefore, our objective was to explore potential targets within the context of intra-tumor heterogeneity (ITH) to modulate the response of tumor-associated macrophages (TAMs) to treatment in BC patients. The TCGA database was used to integrate and analyze human BC samples, from which the ITH score was extracted to identify genetic differences. Using non-negative matrix factorization clustering analysis, we successfully identified two distinct molecular subtypes, referred to as C1 and C2. Notably, subtype C1 exhibited a significantly more favorable prognosis compared with subtype C2. Further investigation of immune cell infiltration using the CIBERSORT algorithm revealed a significant correlation between both subtypes and the infiltration of TAMs. Additionally, we identified SPIB as a key factor influencing TAM infiltration within the model. Notably, SPIB is expressed at low levels in BC and is associated with an unfavorable prognosis for patients. Interestingly, overexpression of SPIB led to increased infiltration of M1 macrophages. In conclusion, this study sheds light on the characteristics of BC and immune cell infiltration within its microenvironment. SPIB emerges as a promising therapeutic candidate, with potential to modulate the immunosuppressive nature of the BC microenvironment and improve patient outcomes.