ArticleBritish journal of cancer2025
Oncogenic NFE2L2 mutations in plasma ctDNA and tumors are predictors and prognosticators of chemoradiation therapy in resectable esophageal squamous cell carcinoma.
Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Pleural Mesothelioma With Unusual Squamous Differentiation: A Clinicopathological Case Report With Molecular Insights From Whole-Exome Sequencing.Pathology international · 2026Article
- Circulating Tumor DNA for Minimal Residual Disease Detection and Recurrence Prediction in Upper Gastrointestinal Cancers: A Scoping Review.Journal of clinical medicine · 2026Review
- Nrf2 deficiency converts the ESCC microenvironment into an immunologically active state via the GPX2-ICD-DC signaling path.Journal of translational medicine · 2026Article
- Narrative review: clinical application and challenges of circulating tumor DNA in treatment response evaluation and prognostic prediction for esophageal cancer.Journal of thoracic disease · 2026Review
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Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe poor prognosis of resectable esophageal squamous cell carcinoma (ESCC) poses an unmet need to identify early predictive and prognostic genomic biomarkers to improve treatment outcome and risk stratification.
methodsMutational profiling was performed for 171 ESCC patients receiving curative neoadjuvant chemoradiation treatment (nCRT). The discovery cohort included 100 ESCC formalin-fixed paraffin-embedded (FFPE) tumor specimens; the validation FFPE cohort consisted of serial ctDNA samples from 71 patients.
resultsThe discovery cohort identified hot-spot oncogenic NFE2L2 mutations exclusively localized at DLG and ETGE KEAP1-binding motifs in poor responders associated with incomplete pathological response (P = 0.004). Patients with NFE2L2 mutations in two independent FFPE cohorts had about 2-fold higher risk of death and recurrence. Serial ctDNA analysis further demonstrated oncogenic NFE2L2 mutations detected at post-nCRT were independent prognosticators for recurrence (HR = 5.90; P = 0.005) and survival (HR = 4.75; P = 0.013). Risk stratification based on pathological T and N stages, positive FFPE (HR = 4.50) and ctDNA NFE2L2 mutations (HR = 8.50) identified high-risk groups for recurrence (P = 0.001). Combined FFPE and ctDNA NFE2L2 mutation status predicted nCRT responses (P = 0.05) by ROC analysis.
conclusionsTracking oncogenic NFE2L2 mutations at pre-treatment and post-surgery or serial ctDNA monitoring during treatment are useful nCRT predictors and independent prognosticators of survival for locally advanced ESCC.
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