DAPP1 Elevated Expression Influences Macrophages and Predicts Poor Prognosis in Breast Cancer

Purpose The main purpose of this study is to clarify the intricate regulatory pathways in the breast cancer tumor microenvironment, with a specific focus on revealing the immunological relevance and prognostic significance of the adaptor protein DAPP1 (dual adaptor of phosphotyrosine and 3-phosphoinositides 1) in the breast cancer microenvironment. The core research question is to determine how DAPP1 influences breast cancer progression, particularly its association with immune-related factors and patient outcomes. Methods This study adopted an integrated research approach, including bioinformatics analysis, clinical tissue microarray verification, and molecular experiments. Multiplex immunohistochemistry was used to quantitatively assess the expression level of DAPP1 and analyze its correlation with tumor-infiltrating immune cells (such as specific macrophage subsets) and immune checkpoints. Western blotting was employed to identify the protein expression of DAPP1 in cell lines, and stable knockdown and overexpression models of DAPP1 were constructed. Functional validation was performed using Cell Counting Kit-8 assay to detect cell proliferation ability and Transwell assay to detect migration and invasion abilities. Results The study found that DAPP1 was significantly highly expressed in breast cancer tissues and independently associated with advanced clinical stages and poor overall survival. In addition, the expression level of DAPP1 was positively correlated with the infiltration of CD68⁺CD86⁺ macrophages and the expression of CTLA4. Functional analyses further confirmed that DAPP1 could enhance the proliferation, migration, and invasion abilities of breast cancer cells. Conclusion These findings indicate that DAPP1 promotes the development of breast cancer by enhancing the malignant phenotypes of tumor cells and creating an immunosuppressive microenvironment. Therefore, DAPP1 can serve as a valuable prognostic indicator and a potential therapeutic target.