DSTYK predicts Chemoresistance in Triple-Negative Breast Cancer Patient-Derived Xenograft Models

Patient-derived xenograft (PDX) models are widely regarded as robust preclinical platforms because they preserve the histopathological and molecular features of primary tumors. In this study, we established twenty triple-negative breast cancer (TNBC) PDX models using freshly resected patient tumors, including ten with high DSTYK expression and ten with low DSTYK expression. Tumor fragments were orthotopically implanted into the fourth mammary fat pads of NSG mice. DSTYK expression was validated by immunohistochemistry and western blotting. Histological evaluation across three serial passages demonstrated that PDX tumors retained the cellular morphology, stromal architecture, and lineage characteristics of their corresponding primary tumors. Using these models, we assessed in vivo responses to combination chemotherapy with doxorubicin and docetaxel. DSTYK-low PDX tumors exhibited significantly greater chemosensitivity, whereas DSTYK-high tumors showed marked resistance, indicating a critical role for DSTYK in mediating chemotherapy resistance. Consistent with these findings, analyses from The Human Protein Atlas and Kaplan-Meier Plotter databases revealed that high DSTYK expression is associated with poor survival outcomes in TNBC patients. Collectively, our results from clinical specimens, PDX models, and public datasets identify DSTYK as a promising prognostic biomarker and predictor of chemotherapeutic response in TNBC, with potential implications for patient stratification and treatment optimization.