STAMBP as a potential contributor of docetaxel resistance and prognostic biomarker in breast cancer

Background: Breast cancer continues to be a leading cause of cancer-related mortality among women worldwide, with resistance to docetaxel posing a major therapeutic challenge. STAMBP , a deubiquitinating enzyme from the JAMM family, plays a key role in maintaining proteostasis through ubiquitin cleavage; however, its involvement in docetaxel resistance and its potential as a prognostic biomarker have not been fully explored. Objectives: This study aimed to investigate the relationship between STAMBP and docetaxel resistance, assess its prognostic relevance in breast cancer, and identify potential therapeutic strategies targeting STAMBP to improve treatment outcomes. Methods: We used the DepMap platform to examine the role of STAMBP in docetaxel resistance through Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) knockout screening across 45 breast cancer cell lines. Gene Set Enrichment Analysis was performed to explore associated pathways. The prognostic value of STAMBP was analyzed using data from TCGA, the Human Protein Atlas, and GEO. Potential therapeutic strategies were identified through integrated analysis of siRNA screens based on the GDSC and PRISM Repurposing datasets. Results: STAMBP expression was positively correlated with docetaxel resistance, and its knockout reduced cell viability in 80% (36/45) of the tested cell lines. STAMBP -associated pathways were primarily involved in cell cycle and DNA repair mechanisms. Clinical analyses revealed that STAMBP was upregulated in tumor tissues and correlated with worse overall and relapse-free survival. Moreover, breast cancer cells with high siRNA efficacy against STAMBP exhibited increased sensitivity to docetaxel compared with those with low efficacy. Conclusion: These findings suggest that STAMBP is a potential contributor to docetaxel resistance and an independent prognostic biomarker in breast cancer. Targeting STAMBP may be a promising strategy to overcome chemoresistance, warranting further investigation into its molecular mechanisms and therapeutic potential.