Hypoxia-induced up-regulation of apelin is associated with a poor prognosis in oral squamous cell carcinoma patients

Oral Oncol. 2012 Jun;48(6):500-6. doi: 10.1016/j.oraloncology.2011.12.015. Epub 2012 Jan 28.


Recently, apelin has been shown to be a novel angiogenic factor in various cancers including lung, breast and brain cancer. However, there is limited information regarding the expression and role of apelin in oral cavity cancer. In this study, we determined that apelin expression was localized in the cytoplasm of oral squamous cell carcinoma at various intensities. Strong apelin expression significantly correlated with tumor recurrence and disease-free survival. Using a multivariate analysis, we demonstrated that apelin was an independent prognostic factor for on disease-free survival, age, lymph node metastasis and CA9 expression. Moreover, apelin expression was up-regulated under hypoxic conditions, and exogenous apelin enhanced the proliferation and migration of oral cancer cells. Based on these results, we propose that the presence of hypoxia-induced apelin is a new prognostic factor and potential therapeutic target for oral squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism
  • Apelin
  • Blotting, Western
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / surgery
  • Cell Hypoxia
  • Cytoplasm / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / surgery
  • Neoplasm Recurrence, Local / metabolism*
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism
  • Young Adult


  • APLN protein, human
  • Actins
  • Antigens, Neoplasm
  • Apelin
  • Intercellular Signaling Peptides and Proteins
  • Vascular Endothelial Growth Factor A
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases