Scholarlink

Background <p>Precision 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).</p> Methods <p>This 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.</p> Results <p>Among 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 <i>TP53</i>, followed by <i>CDKN2A</i> and <i>NFE2L2</i>. The frequency of <i>NFE2L2</i> mutations was significantly higher in the middle thoracic region (<i>P</i> = 0.041). The mutation rate increased from Stage I to IV (<i>P</i> = 0.0046). <i>NFE2L2</i> 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 <i>NFE2L2</i> mutations. The overall survival of patients with unresectable or metastatic ESCC harboring <i>NFE2L2</i> mutations was 12.0&#xa0;months, compared to 29.7&#xa0;months in patients without the mutations (HR: 2.37, <i>P</i> = 0.047).</p> Conclusion <p><i>NFE2L2</i> mutations were more common in the middle thoracic esophagus, appeared to be associated with tumor progression, and were linked to poor prognosis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Site-specific prevalence of the NFE2L2 mutation in esophageal squamous cell carcinoma

  • 期刊论文

  • 发表日期：

    2025年10月29日

查看全文
  • Akihiko Chida,
  • Hideyuki Hayashi,
  • Norihito Ishida,
  • Eiichiro So,
  • Shotaro Kishimoto,
  • Sara Horie,
  • Kai Tsugaru,
  • Satoru Matsuda,
  • Hirofumi Kawakubo,
  • Hiroshi Nishihara,
  • Yasuo Hamamoto,
  • Takanori Kanai,
  • Yuko Kitagawa,
  • Kenro Hirata

摘要

Background

Precision 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).

Methods

This 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.

Results

Among 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).

Conclusion

NFE2L2 mutations were more common in the middle thoracic esophagus, appeared to be associated with tumor progression, and were linked to poor prognosis.