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Cancer FerroptosisCancer Drug Resistance

The ferroptotic effect of NRF2-GCLM signaling axis in esophageal squamous cell cancer: in vivo study

Scientific Reports

Abstract

This study investigates the role of NRF2 in esophageal squamous cell carcinoma from in vivo and clinical perspectives. Analysis of 61 biopsies found elevated NRF2, GCLM, and GPX4 expression in ESCC. GCLM overexpression conferred radiotherapy resistance.

Key Findings

  • NRF2, GCLM, GPX4 significantly elevated in esophageal cancer vs normal tissue
  • High NRF2/GCLM/GPX4 correlates with metastasis and poor prognosis
  • GCLM identified as key NRF2 downstream target for radiotherapy resistance
  • Clinical data from 61 patient biopsies

Clinical Significance

Extends NRF2-ferroptosis findings to esophageal cancer with clinical patient data. Identifies GCLM as novel biomarker for radiotherapy resistance.

Citation

Nuerrula, Y. et al. (2025). NRF2-GCLM in esophageal cancer. Scientific Reports.

DOI: 10.1038/s41598-025-10414-2