Integrated Single-Cell and Bulk RNA Sequencing Identifies SERPING1 as a Biomarker of Immune Infiltration and Prognosis in Triple-Negative Breast Cancer.

[BACKGROUND] Triple-negative breast cancer (TNBC) is an aggressive malignancy that lacks effective treatment. Immune infiltration plays an important role in anti-tumor responses. Serpin family G1 (), a biomarker associated with immune infiltration, has been implicated in multiple cancers, but its role in TNBC remains unclear.

[METHODS] RNA sequencing and clinical data for TNBC were obtained from the Gene Expression Omnibus, the Cancer Genome Atlas, and the Molecular Taxonomy of Breast Cancer International Consortium databases. First, the expression, prognostic value, and biological functions of were analyzed. Then, the tumor microenvironment (TME) was comprehensively characterized, and the relationship between expression and immunotherapy response was assessed. Immunohistochemical staining was performed to confirm SERPING1 expression and the abundance of CD4+ T cells and CD8+ T cells in clinical specimens. Finally, single-cell analysis was conducted to investigate the role of in immune cell activation.

[RESULTS] was downregulated in TNBC and was an independent predictor of survival. Functionally, activated the immune response in TNBC patients. Mechanistically, elevated levels lead to increased immune cell infiltration, particularly of CD4+ and CD8+ T cells, in the TME. Moreover, was primarily localized in cancer-associated fibroblasts (CAFs), with SERPING1+ apCAFs exhibiting increased communications with anti-tumor immune cells at the single-cell level.

[CONCLUSIONS] contributes to enhanced immune cell infiltration, desirable immunotherapy response, and improved prognosis. It thus can be utilized as a promising biomarker for immune infiltration and prognosis. These findings provide novel insights into TME-related immune regulation and may inform strategies to enhance immunotherapy efficacy in TNBC.