Forkhead-box A1 transcription factor is a novel adverse prognosis marker in human glioma

J Clin Neurosci. 2013 May;20(5):654-8. doi: 10.1016/j.jocn.2012.03.055. Epub 2013 Mar 16.

Abstract

Forkhead-box A1 (FOXA1), a member of the FOX family of transcription factors, has been implicated in certain tumor types including breast, prostate, lung, thyroid and esophageal squamous cell carcinomas. The aim of this study was to investigate the clinicopathological significance of FOXA1 expression in human malignant glioma. FOXA1 expression in human glioma and non-neoplastic brain tissue was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry. The association of FOXA1 immunostaining with clinicopathological factors and prognosis in patients with glioma was also investigated. The expression levels of FOXA1 messenger RNA (mRNA) and protein in glioma tissues were significantly higher than those in corresponding non-neoplastic brain tissue (both p<0.001). In addition, the expression of FOXA1 was upregulated in high-grade glioma tissue compared with that in low-grade tissues, and increased with ascending World Health Organization (WHO) tumor grade (p=0.001). The increased expression of FOXA1 protein was also significantly correlated with low Karnofsky performance scale score (p=0.02). Moreover, the overall survival rate for patients with high FOXA1 protein expression was clearly lower than that for patients with low FOXA1 protein expression (p=0.01). Multivariate analysis showed that high FOXA1 protein expression was an independent prognostic factor for overall survival (p=0.02) in patients with glioma. In conclusion, our results suggest, for the first time, that FOXA1 might be a potential regulator of progression of human glioma and its upregulation might be closely associated with a poor clinical outcome for patients with this serious disease.

MeSH terms

  • Adult
  • Aged
  • Astrocytoma / metabolism
  • Astrocytoma / surgery
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / classification
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / surgery
  • Female
  • Follow-Up Studies
  • Glioblastoma / metabolism
  • Glioblastoma / surgery
  • Glioma / classification
  • Glioma / metabolism*
  • Glioma / surgery
  • Hepatocyte Nuclear Factor 3-alpha / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Karnofsky Performance Status
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / metabolism
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Hepatocyte Nuclear Factor 3-alpha
  • RNA, Messenger