Significance of nuclear accumulation of Foxo3a in esophageal squamous cell carcinoma

Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):1220-9. doi: 10.1016/j.ijrobp.2008.02.077.


Purpose: To investigate the value of Foxo3a in predicting the response to neoadjuvant treatment of, and prognosis for, esophageal squamous cell carcinoma.

Methods and materials: Immunohistochemical staining was performed in a retrospective series of 60 biopsied esophageal squamous cell carcinomas, and the correlation between nuclear accumulation of Foxo3a and clinicopathologic features was analyzed, including patient survival. In addition, in vitro biologic changes, radiosensitivity, and in vivo tumorigenicity of esophageal carcinoma cells after experimental manipulation of Foxo3a expression levels were determined.

Results: Clinical findings point to a significant correlation between the nuclear accumulation of Foxo3a and the survival rate of esophageal cancer patients. In addition, Foxo3a is a significant predictor for the response to neoadjuvant therapy. In cell culture, irradiation and oxidative stress seemed to result in nuclear accumulation of Foxo3a. Down-regulation of Foxo3a significantly decreased radiosensitivity but had no obvious effect on tumor growth, as measured by a clonogenic assay in vitro and growth delay in vivo.

Conclusions: Nuclear accumulation of Foxo3a in tumor cells was correlated with increased radiosensitivity and with improved patient survival. Thus, it is suggested that Foxo3a may be a potential marker for esophageal cancer.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / therapy*
  • Cell Nucleus / metabolism*
  • Esophageal Neoplasms / diagnosis
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / therapy*
  • Female
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Prognosis
  • Retrospective Studies
  • Statistics as Topic
  • Treatment Outcome


  • Biomarkers, Tumor
  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors