Multi-omics bioinformatic screening identifies PFDN2 as an obesity-correlated molecular target of triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC) is characterized by high malignancy, poor prognosis and a lack of specific therapeutic targets. Obesity acts as a major risk factor facilitating TNBC progression, while the molecular features underlying their correlation remain poorly systematically characterized. In this study, we integrated single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic datasets from the GEO database to screen candidate genes consistently changed in both obesity and TNBC. We constructed single-cell atlases, performed cell type annotation and analyzed intercellular communication networks using Seurat, SingleR and CellChat, respectively. PFDN2 was identified via intersection analysis of differentially expressed genes (DEGs). Functional experiments including qRT-PCR, siRNA transfection, CCK-8 and EDU proliferation assays verified that PFDN2 silencing markedly suppresses the proliferation of TNBC cells. Collectively, this study identified PFDN2 as a gene consistently changed both in obesity and TNBC. It provides novel insights into the molecular mechanisms of obesity-associated TNBC, and indicates that PFDN2 holds research potential as a molecular target and candidate therapeutic target.