Adipokines in Neuroendocrine Tumors: An Evaluation of the Serum Levels of Ghrelin and Leptin

Abstract

Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that are characteristically different from other malignancies. The difference is not only in the prognosis, which is usually more favorable in such patients, but also in the high clinical progression of the disease, where NET patients do not experience the cachexia typical of other malignancies. The purposes of this study were to evaluate the ghrelin and leptin levels in a group of patients diagnosed with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and bronchopulmonary neuroendocrine tumors (BP-NETs) and to analyze the relationship between the body mass index (BMI), cachexia and selected NET markers. The study group comprised 52 patients with GEP-NETs and BP-NETs, while the controls comprised 67 healthy volunteers. The ghrelin and leptin concentrations were determined in both groups. The concentrations of chromogranin A, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), total cholesterol, triglycerides and glucose were determined in the study group. Characteristics of the study group and of the controls were defined by age, sex and BMI, and the effects of these factors on the ghrelin and leptin concentrations were assessed. The data obtained were subject to statistical analysis. The study cohort showed higher levels of ghrelin as compared to the controls (142.31 ± 26.00 vs. 121.49 ± 35.45, p = 0.016), and no statistical difference in the levels of leptin (11.15 ± 9.6 vs. 12.94 ± 20.30, p = 0.439) were observed. Significantly lower levels of leptin were found in patients with the small intestine primary location, as compared to individuals with primary locations in the lungs and the pancreas (4.9 ± 6.49 vs. 16.97 ± 15.76, p = 0.045, and 4.9 ± 6.49 vs. 12.89 ± 8.56, p = 0.016, respectively). A positive correlation was observed between the leptin levels and the BMIs in both the study group (r_S = 0.33, p = 0.016) and the controls (r_S = 0.41, p = 0.001). The study group showed a negative correlation between the leptin levels and 5-HIAA (r_S = -0.32, p = 0.026) and a negative correlation between the leptin levels and Ki-67 (r_S = -0.33, p = 0.018). The control group showed negative correlations between the ghrelin and the volunteer age (r_S = -0.41, p = 0.008), the leptin and the volunteer age (r_S = -0.44, p < 0.001), the leptin and total cholesterol (r_S = -0.24, p < 0.049) as well as the leptin and triglycerides (r_S = -0.33, p < 0.006). The current study emphasized the importance of the markers' determination, where ghrelin appears as a valuable diagnostic biomarker in NETs, probably responsible for maintaining a normal BMI, despite the progression of the disease.

Keywords: adipokines; cachexia; ghrelin; leptin; neuroendocrine tumors.

Figure 1

Mean leptin levels with standard deviations in patients with various primary site locations. * Locations with leptin levels significantly higher than the small intestine (SINET) levels. ** Locations with leptin levels significantly lower than those in lung and pancreas primary tumors.

Figure 2

Workflow demonstrating inclusion and exclusion of patients and healthy volunteers in study and control groups.