Apelin beyond kidney failure and hyponatremia: a useful biomarker for cancer disease progression evaluation

Clin Exp Med. 2015 Feb;15(1):97-105. doi: 10.1007/s10238-014-0272-y. Epub 2014 Jan 28.


Apelin regulates angiogenesis, stimulating endothelial cell proliferation and migration. It is upregulated during tumor angiogenesis, and its overexpression was reported to increase tumor growth. Furthermore, apelin controls vasopressin release and body fluid homeostasis. The aim of this study was to examine the correlations between apelin expression and clinical outcomes in oncologic patients, such as cancer disease progression and patient's survival. Apelin levels were evaluated in a cohort of 95 patients affected by different varieties of cancer. Partial remission and stable disease were assigned to the 'no progression' group, comparing it with the progressor group. Patients were followed up for 2 years. Receiver operating characteristics analysis was employed for identifying the progression of the oncologic disease and Kaplan-Meier curves assessed the survival. Adjusted risk estimates for progression endpoint were calculated using Cox proportional hazard regression analysis. Oncologic patients had higher apelin levels compared with healthy subjects, and apelin was closely related to the stages of the disease. In the hyponatremia group, apelin values were significantly higher than patients with eunatremia. After the follow-up of 24 months, 41 patients (43%) reached the endpoint. Progressor subjects presented significantly increased apelin values at baseline compared with non-progressor. Univariate followed by multivariate Cox proportional hazard regression analysis showed that apelin predicted cancer progression independently of other potential confounders. In patients with cancer, apelin closely reflects the stage of the disease and represents a strong and independent risk marker for cancer progression.

MeSH terms

  • Aged
  • Apelin
  • Biomarkers, Tumor / genetics*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Expression
  • Humans
  • Hyponatremia / complications
  • Hyponatremia / diagnosis*
  • Hyponatremia / genetics
  • Hyponatremia / mortality
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms / complications
  • Neoplasms / diagnosis*
  • Neoplasms / genetics
  • Neoplasms / mortality
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Renal Insufficiency / complications
  • Renal Insufficiency / diagnosis*
  • Renal Insufficiency / genetics
  • Renal Insufficiency / mortality
  • Risk
  • Survival Analysis


  • APLN protein, human
  • Apelin
  • Biomarkers, Tumor
  • Intercellular Signaling Peptides and Proteins