TCF19 Is Overexpressed and Exerts Oncogenic Effects in Breast Cancer: A Bioinformatic and In Vitro Study

Breast cancer is the most common malignancy in women and a major cause of cancer-related deaths, yet effective biomarkers that predict progression and guide therapy remain limited. This study explored the role of Transcription Factor 19 (TCF19) in breast cancer using public multi-omics datasets and in vitro functional assays. We first assessed TCF19 expression and its clinical associations and analysed co-expressed genes through network construction and pathway enrichment. We then evaluated immune cell infiltration, and examined proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) in breast cancer cell lines following TCF19 knockdown. A prognostic nomogram integrating TCF19 with clinical variables was also constructed. TCF19 was significantly overexpressed in breast cancer at both mRNA and protein levels. High TCF19 expression correlated with aggressive features, including larger tumour size, HER2 positivity, hormone receptor negativity, and high MKI67 expression, and was associated with poorer overall, disease-specific, and progression-free survival in univariate analyses, with the strongest association observed in HER2-positive patients. TCF19-related genes were mainly involved in cell-cycle regulation and chromosome segregation, and elevated TCF19 was associated with increased immunosuppressive cell infiltration and reduced CD8+ T cells and natural killer (NK) cells. In vitro, TCF19 silencing reduced CDK1 levels, impaired proliferation, migration, and invasion, and reversed EMT. Although the TCF19-containing nomogram showed encouraging internal calibration (C-index = 0.762), TCF19 did not remain an independent prognostic factor after adjustment for clinical confounders. Overall, our findings indicate that TCF19 is a candidate prognostic biomarker and potential therapeutic target in breast cancer that warrants independent clinical and in vivo validation.