Integrated single-cell and bulk RNA sequencing identifies SERPING1 as an immune infiltration regulator and therapeutic target 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 activating anti-tumor responses. This study aims to identify regulators of immune infiltration and potential therapeutic targets for TNBC. Methods Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data were obtained from Gene Expression Omnibus, The Cancer Genome Atlas, and Molecular Taxonomy of Breast Cancer International Consortium databases. Serpin family G1 (SERPING1) was identified as a regulator of immune infiltration using weighted gene co-expression network analysis. First, the expression, prognostic value and biological functions of SERPING1 were analyzed. Then, tumor microenvironment (TME) in TNBC was comprehensively characterized and the relationship between SERPING1 expression and immunotherapy response was assessed. Additionally, immunohistochemical staining was performed to confirm SERPING1 expression and the abundance of CD4 + and CD8 + T cells in clinical specimens. Finally, the role of SERPING1 in immune cell activation was explored through cell communication analysis. Results SERPING1 was identified as a critical regulator linked to enhanced immune cell infiltration in TNBC. Clinically, SERPING1 was downregulated in TNBC and was an independent predictor of survival. Functionally, SERPING1 activated the immune response in TNBC patients. Mechanistically, elevated SERPING1 levels lead to higher immune cell infiltration, particularly of CD4 + and CD8 + T cells in TME. Moreover, SERPING1 was primarily localized in fibroblasts, with SERPING1 + fibroblasts exhibiting increased communications with anti-tumor immune cells at the single-cell level. Conclusions SERPING1 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, as well as a potential therapeutic target in TNBC.