Significance of nuclear accumulation of Foxo3a in esophageal squamous cell carcinoma.
OBJECTIVE
To investigate the value of Foxo3a in predicting the response to neoadjuvant treatment of, and prognosis for, esophageal squamous cell carcinoma.


METHODS
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.
Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan. miaofen@adm.cgmh.org.tw
Miao-Fen
MF
Chen
Fu-Min
FM
Fang
Chang-Hsien
CH
Lu
Ming-Shian
MS
Lu
Wen-Cheng
WC
Chen
Kuan-Der
KD
Lee
Paul-Yang
PY
Lin
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy*; D002467:Cell Nucleus / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy*; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012189:Retrospective Studies; D013223:Statistics as Topic; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors