Integrated analysis reveals ferroptosis suppression as a key factor in chemoradiotherapy resistance in muscle-invasive bladder cancer, indicating personalized treatment approaches.
Key Points
The study aims to identify molecular factors influencing resistance to chemoradiotherapy in muscle-invasive bladder cancer and explore the role of ferroptosis suppression.
Conducted transcriptomic profiling of pre-treatment tumors from 179 patients undergoing bladder-preserving treatment.
Utilized bladder cancer cell models for RNA sequencing, lipidomic profiling, and CRISPR/Cas9 screening to identify molecular determinants of resistance.
Analyzed correlations between ferroptosis suppressor gene expression and clinical outcomes.
Patients with high ferroptosis suppressor signature exhibited poorer responses to chemoradiotherapy and shorter survival times.
Ferroptosis suppression was associated with immune-excluded microenvironments and distinct transcriptional patterns.
CRISPR/Cas9 screening identified key genes related to ferroptosis suppression that are potential targets for enhancing radiosensitivity.