Loss of FOXF2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma Patients

Ann Surg Oncol. 2016 Jan;23(1):211-7. doi: 10.1245/s10434-015-4515-2. Epub 2015 Mar 31.


Background: FOXF2 is a member of the forkhead box (FOX) family of transcription factors. FOXF2 plays an important role in several tumors but its expression and role in hepatocellular carcinoma (HCC) remains unknown.

Methods: Using immunohistochemistry, western blot, and real-time polymerase chain reaction, we analyzed FOXF2 expression in 295 clinicopathologically characterized HCC cases. Using RNA interference (RNAi), we investigated the effects of FOXF2 depletion on tumor cell behavior in vitro. Statistical analyses were used to determine associations between FOXF2 levels, tumor features, and patient outcomes.

Results: FOXF2 downregulation was observed in HCC tissues (p < 0.001) compared with peritumorous tissues, and its expression levels were closely correlated with overall survival and recurrence-free survival (p = 0.023 and 0.006, respectively) in patients with HCC. RNAi-mediated silencing of the FOXF2 gene in the MHCC-97H cell line significantly promoted proliferation and anti-apoptosis.

Conclusions: The results of the present study indicate that FOXF2 may serve as a prognostic biomarker for HCC and may be a promising target in the treatment of patients with HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Biomarkers, Tumor
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / surgery
  • Cell Proliferation
  • Female
  • Follow-Up Studies
  • Forkhead Transcription Factors / antagonists & inhibitors
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / surgery
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Tumor Cells, Cultured


  • Biomarkers, Tumor
  • FOXF2 protein, human
  • Forkhead Transcription Factors
  • RNA, Messenger
  • RNA, Small Interfering