Abstract 3942: NRF2 pathway activation predicts poor radiation response in laryngeal cancer: Insights from a large proteogenomic characterization study.

Key Points

• To investigate how NRF2 pathway activation affects clinical outcomes in laryngeal cancer patients receiving radiation therapy or surgery.
• Characterized tumor samples using RNA sequencing and mass spectrometry-based proteomics.
• Calculated an NRF2 activity score to classify tumors based on NRF2 activity.
• Conducted Kaplan-Meier analysis and Cox proportional hazards modeling to evaluate disease-free survival and locoregional failure rates.
• Analyzed gene and protein expression for NRF2-induced targets associated with locoregional failure.
• Performed logistic regression to determine predictive factors for radiation-treated patients.
• NRF2-high patients demonstrated significantly worse outcomes than NRF2-low patients after radiation treatment.
• Five-year locoregional failure rates were 51.0% for NRF2-high and 17.1% for NRF2-low patients.
• Five-year disease-free survival rates were 25.4% for NRF2-high versus 50.7% for NRF2-low patients.
• NRF2 activation was not a significant prognostic factor in patients treated with surgery alone.
• Upregulation of pathways related to antioxidant response and DNA repair was found in NRF2-high tumors.