Plasma acylated and plasma unacylated ghrelin: useful new biomarkers in patients with neuroendocrine tumors?

Abstract

To date, the value of fasting plasma acylated ghrelin (AG) and unacylated ghrelin (UAG) as potential novel biomarkers in patients with neuroendocrine tumors (NETs) is unknown. The aims of this study are to (i) compare fasting AG and UAG levels between nonobese, nondiabetic NET patients (N=28) and age- (±3 years) and sex-matched nonobese, nondiabetic controls (N=28); and (ii) study the relationship between AG, UAG, and AG/UAG ratios and biochemical (chromogranin-A (CgA) and neuron-specific enolase (NSE) levels) and clinical parameters (age at diagnosis, sex, primary tumor location, carcinoid syndrome, ENETS TNM classification, Ki-67 proliferation index, grading, prior incomplete surgery) in NET patients. Fasting venous blood samples (N=56) were collected and directly stabilized with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride after withdrawal. Plasma AG and UAG levels were determined by ELISA. Expression of ghrelin was examined in tumor tissue by immunohistochemistry. There were no significant differences between NET patients and controls in AG (median: 62.5 pg/mL, IQR: 33.1–112.8 vs median: 57.2pg/mL, IQR: 26.7–128.3, P=0.66) and UAG in levels (median: 76.6pg/mL, IQR: 35.23–121.7 vs median: 64.9, IQR: 27.5–93.1, P=0.44). No significant correlations were found between AG, UAG, and AG/UAG ratios versus biochemical and clinical parameters in NET patients with the exception of age at diagnosis (AG: ρ= −0.47, P=0.012; AG/UAG ratio: ρ= −0.50, P=0.007) and baseline chromogranin-A levels (AG/UAG ratio: ρ= −0.44, P=0.019). In our view, fasting plasma acylated and unacylated ghrelin appear to have no value as diagnostic biomarkers in the clinical follow-up of patients with NETs.

Plasma levels of acylated ghrelin in patients with insulinoma and expression of ghrelin and its receptor in insulinomas

“…The difference could be due to the different tumor types between our study (insulinoma only) and theirs [42]. The plasma levels of acylated ghrelin did not correlate with clinicopathological characteristics which is consistent with previous findings [44].…”

“…These researchers suggested that it was worthwhile to test acylated ghrelin levels in patients with NETs [41,42]. A recent study on NETs compared fasting acylated ghrelin and unacylated ghrelin levels between NET patients and controls, showed that there was no significant difference between patients and controls in fasting acylated ghrelin but only three patients with PNETs were included and, obese patients and obese matched controls were excluded in this study [44].…”

The Acylated/Unacylated Ghrelin Ratio Is Similar in Patients With Acromegaly During Different Treatment Regimens

“…This is considerably lower than levels that have been observed in healthy control subjects, measured using equivalent two-site sandwich assays and stabilized with AEBSF. Adrichem et al (40) found median plasma AG levels of 57.2 pg/mL (range, 10 to 273 pg/mL) and median plasma UAG levels of 64.9 pg/mL (range, 8 to 331 pg/mL) in 28 healthy control subjects, whereas Liu et al (53) reported AG levels ranging from 43 to 366 pg/mL in four healthy volunteers.…”

“…All patients gave their written informed consent, and the study was approved by the Medical Ethics Committee of Erasmus University MC, Rotterdam. (39,40).…”

Ghrelin and its role in gastrointestinal tract tumors (Review)

“…In patients with metastatic disease, the levels of ghrelin were elevated, compared with the control group, in up to 85% of cases ( 157 ). A later study focusing on the active peripheral forms of ghrelin (acylated ghrelin; desacyl ghrelin; acylated ghrelin/desacyl ghrelin ratio) found no statistical difference between patients with NETs and the control group ( 158 ).…”