Expression and prognosis of FOXO3a and HIF-1α in nasopharyngeal carcinoma

J Cancer Res Clin Oncol. 2012 Apr;138(4):585-93. doi: 10.1007/s00432-011-1125-7. Epub 2011 Dec 31.


Purpose: The Forkhead Box O3a transcription factor (FOXO3a) and hypoxia-inducible factor-1α (HIF-1α) have been reported to play important roles in the development and prognosis of human cancers. However, their exact roles are not clear. Therefore, we investigated the expression status and clinical significance of FOXO3a and HIF-1α expression in nasopharyngeal carcinoma.

Methods: The expression of FOXO3a and HIF-1α proteins was detected in nasopharyngeal carcinoma tissues and normal nasopharyngeal tissues by immunohistochemistry and western blot. Furthermore, we analyzed the association of FOXO3a and HIF-1α expression with various clinicopathologic factors including survival status of nasopharyngeal carcinoma patients.

Results: FOXO3a was low expressed and HIF-1α was high expressed in nasopharyngeal carcinoma tissues, compared with normal nasopharyngeal tissues (both P < 0.05). The low expression of FOXO3a was significantly correlated with clinical stage (P = 0.003), T stage (P = 0.011), lymph node metastasis (P = 0.003), and distant metastasis (P = 0.030), and over expression of HIF-1α was significantly correlated with T stage (P = 0.026), lymph node metastasis (P = 0.002), and distant metastasis (P = 0.010). The Spearman analysis indicated that FOXO3a expression was inversely correlated with HIF-1α expression(rs = -0.598, P < 0.001). Overall survival curves estimated by Kaplan-Meier showed that tumor patients with low FOXO3a or high HIF-1α expression had significantly poorer prognosis compared with patients with high FOXO3a or low HIF-1α levels (P < 0.001, and P = 0.012, respectively). In addition, multivariate Cox regression analysis showed that T stage, distant metastasis, and FOXO3a were significant independent prognostic factors for overall survival (P = 0.011, P = 0.008, and P = 0.047, respectively).

Conclusions: Our results suggested that FOXO3a and HIF-1α may be considered to be important prognostic markers in nasopharyngeal carcinoma.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis
  • Blotting, Western
  • Carcinoma
  • Female
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / biosynthesis*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharynx / metabolism
  • Neoplasm Staging
  • Prognosis


  • Biomarkers, Tumor
  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • Hypoxia-Inducible Factor 1, alpha Subunit