ArticleInternational journal of clinical oncology2025
Site-specific prevalence of the NFE2L2 mutation in esophageal squamous cell carcinoma.
Article in International journal of clinical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPrecision medicine for esophageal squamous cell carcinoma (ESCC) has not been implemented owing to a lack of site-specific therapeutic markers and biomarkers. We hypothesized that the genomic background of each subsite of the esophagus might be different, allowing us to develop site-specific treatment strategies (cervical, upper thoracic, middle thoracic and lower thoracic).
methodsThis was a single-center retrospective cohort study. Patients diagnosed with ESCC who underwent comprehensive genomic profiling (CGP) at Keio University Hospital between April 2017 and March 2024 were recruited. Genomic profiles were analyzed and compared across esophageal subsites.
resultsAmong the 107 patients with ESCC who underwent CGP, 6 were cervical, 16 were upper thoracic, 54 were middle thoracic, and 31 were lower thoracic. The most frequently altered genes were TP53, followed by CDKN2A and NFE2L2. The frequency of NFE2L2 mutations was significantly higher in the middle thoracic region (P = 0.041). The mutation rate increased from Stage I to IV (P = 0.0046). NFE2L2 mutations were rarely observed in early-stage cancers, suggesting that they may subsequently be acquired during growth and metastasis. Furthermore, a significant association was observed between a history of heavy alcohol consumption and NFE2L2 mutations. The overall survival of patients with unresectable or metastatic ESCC harboring NFE2L2 mutations was 12.0 months, compared to 29.7 months in patients without the mutations (HR: 2.37, P = 0.047).
conclusionNFE2L2 mutations were more common in the middle thoracic esophagus, appeared to be associated with tumor progression, and were linked to poor prognosis.
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