Integrated Analysis Reveals ZNF184 as a Novel Regulator of Stemness‐Associated Paclitaxel Resistance and Tumor Progression in Breast Cancer

Chemotherapy resistance is the primary cause of clinical treatment failure and unfavorable prognosis among breast cancer patients. Consequently, the exploration of novel molecular targets for chemotherapy resistance is warranted. Here, we demonstrated that Zinc Finger Protein 184 (ZNF184) facilitates chemoresistance in breast cancer. Through integrated bioinformatics and experimental validation, we identified that ZNF184 was highly expressed in paclitaxel-resistant breast cancer cells. Knockdown of ZNF184 inhibited cell proliferation and re-sensitized resistant cells to paclitaxel in vitro and in patients-derived organoids (PDOs). Mechanistically, ZNF184 regulates the expression of stemness-related genes CD44, OCT4, Nanog, SOX2, and ALDH1A1, thereby promoting the proliferation of breast cancer cells and subsequent paclitaxel resistance. Pan-cancer analysis revealed the potential of ZNF184 as a prognostic and predictive biomarker for adverse clinical outcomes. Collectively, these findings reveal a previously unknown role of ZNF184 in breast cancer progression and paclitaxel resistance, providing new insights into ZNF184 as a potential therapeutic target for cancer patients.