Prognostic Significance of Preoperative and Postoperative Plasma Levels of Ghrelin in Gastric Cancer: 3-Year Survival Study

Abstract

OBJECTIVES:We aimed to investigate prognostic effects of plasma levels of ghrelin before and after gastrectomy in gastric cancer (GC).METHODS:We followed 81 GC patients up to 3 years in this study. They were candidates for curative gastrectomy with or without neoadjuvant chemotherapy. Plasma levels of total and active ghrelins before and after the operation were assessed. Association of plasma levels of ghrelin with survival were assessed and adjusted for other potential prognostic factors using Cox regression analyses.RESULTS:Both total and active ghrelins dropped after gastrectomy (P<0.001 for both). Multiple Cox models revealed worse survival for patients with postoperative total ghrelins below median (hazards ratio (HR)=2.33, 95% confidence interval (CI): 1.01–5.41) or 25th percentile (HR=4.29, 95% CI: 1.48–12.44) compared with patients with higher ghrelin levels. In case of preoperative total ghrelin, patients with either second or third quartiles of plasma ghrelin showed worse survival compared with patients with the lowest quartile (HR=2.67, 95% CI: 1.11–6.38 for second quartile, and HR=2.32, 95% CI: 1.01–5.35 for third quartile vs. the lowest quartile). However, there was no difference between patients with the highest and lowest quartiles (HR=0.78, 95% CI: 0.22–2.73). Similar pattern was observed for preoperative active ghrelin (HR=4.92, 95% CI: 1.80–13.54 for second quartile, and HR=2.87, 95% CI: 1.11–7.38 for third quartile vs. the lowest quartile). Advanced TNM stage (HR=4.88, 95% CI: 1.10–21.77), cachexia (HR=2.99, 95% CI: 1.35–6.63), and receiving no neoadjuvant chemotherapy (HR=2.02, 95% CI: 1.04–3.92) were other poor prognostic factors.CONCLUSIONS:Preoperative and postoperative plasma levels of ghrelin could predict survival of GC patients with different patterns. This prognostic effect was independent of stage and cachexia. Measurement of plasma ghrelin in GC patients could complement conventional staging for more precise risk-stratification of the patients. Extrinsic admirations of ghrelin after total gastrectomy has potentials to improve survival of GC patients.

Anti-neoplastic effects of aprotinin on human breast cancer cell lines: In vitro study

“…Such clinical evidence further supports potential indications of aprotinin as an antitumor drug. Similar to other recently introduced agents with potential antitumor effects, 34,35 aprotinin could be considered as an adjunct therapy to complement current chemotherapeutic regimens. In addition to enhancing the efficacy, this combination could decrease the dose of chemotherapeutic drugs needed and limit exposure to their numerous unfavorable toxic effects.…”

Attribution of Ghrelin to Cancer; Attempts to Unravel an Apparent Controversy

“…Authors suggested plasma ghrelin in GC is influenced by the extent of the tumor and H. pylori-induced atrophic gastritis. Plasma ghrelin drops significantly after total gastrectomy (50, 65), showing the stomach as the main source of ghrelin. Blood ghrelin recovered to some extent thereafter, suggesting compensatory production of ghrelin from other non-gastric organs (65).…”

“…Higher post-operative plasma ghrelin was linked with better prognosis in GC patients (Table 2; Supplementary Table 3) (50, 105). This survival advantage was independent of stage, grade, cachexia, and tumor size or location.…”

“…This survival advantage was independent of stage, grade, cachexia, and tumor size or location. However, the pre-operative plasma ghrelin showed a different prognostic pattern (50). Patients with either the lowest or highest quartile of plasma ghrelin showed higher survival rates than patients with second-third quartiles.…”

“…Although higher blood ghrelin was associated with decreased incidence of colorectal cancer (46), higher local ghrelin expression in tumor tissue correlated with more aggressive tumors (35). Likewise, although in-vitro studies reported stimulatory effects of ghrelin on proliferation and invasion of gastric cancer cell lines (37, 47), the clinical studies linked ghrelin to a reduced incidence (48, 49), and better prognosis (50). Finally, inconsistencies even exist in the prognostic roles of serum ghrelin measured before or after gastrectomy (50).…”