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

Abstract

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.

Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer

“…In addition, APLN has previously been associated with tumour angiogenesis and survival in other cancer indications. High APLN levels in non-small cell lung cancer patients were correlated with high micro-vessel density [55] and high APLN serum levels were also correlated with disease progression in a study that examined patients that suffered from either lung, gastrointestinal, breast, prostate or gynaecologic cancer [56]. These levels may reflect the state of vascularisation in these tumours and further underlines the importance of APLN during tumour vascularisation.…”

Tumor apelin, not serum apelin, is associated with the clinical features and prognosis of gastric cancer

“…A previous study suggest that tumor patients had higher Apelin levels compared with healthy controls, and Apelin is closely related to the disease stages and progression independently of other potential confounders [ 30 ]. Apelin was expressed in cultured lung cancer cell lines both at the mRNA and protein levels [ 30 ]. We observed similar phenomena in cultured GC cell lines.…”

Tumor angiogenesis: causes, consequences, challenges and opportunities

“…The APLN/APLNR pathway is upregulated in malignant cells in many tumor types [174,176,177], as well as in tumor endothelial cells [178], and elevated Apelin levels are associated with disease progression and poor clinical outcome [176,[179][180][181]. Apelin expression in tumors is regulated by hypoxia [181] and is suggested to promote tumor growth in several ways.…”