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.

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Background: Different prognosis observed for patients of the same clinical stage in gastric cancer, emphasizes the fact that new biological prognostic factors are needed to complement clinical staging. We aimed to investigate the prognostic significance of plasma ghrelin in gastric cancer patients. Methods: In this prospective study, we included 83 gastric cancer patients from Cancer institute of Tehran, Iran. All the patients were candidates for gastrectomy with or without preoperative neoadjuvant chemotherapy (PNC). The patients were followed for three years. Demographic, clinical and para clinical data were registered. Using an ELISA based assay plasma levels of total and active ghrelin were assessed prior to and one week after the operation. Univariate and multivariate COX analyses were used to investigate the independent predictors of patients overall survival. Results: The mean (±SD) age of the patients was 60.3±13.6. Sixty-five (78.3%) patients were male. Majority of the patients had gastric adenocarcinoma (95.2%). Thirty-seven (44.6%) patients had TNM stage II or I. Poorly differentiated grade was detected in 29 (34.9%) of the patients. Forty-eight (57.8%) patients received PNC before the operation. Mean (±SD) survival was 529 ± 373 days. Mean level of the plasma total ghrelin was 269.8±268.7 and 108.7±91.2 (pg/ml) before and after the operation, respectively (P&lt;0.001). Mean level of the plasma active ghrelin was 68.0 ± 63.8 and 44.0± 29.6 (pg/ml) before and after the operation, respectively (P&lt;0.001). Patients in the upper half or highest quartile of postoperative total ghrelin had better survival compared to the corresponding subgroups (Log rank test P = 0.02 and P&lt;0.001, respectively). Multivariate COX model revealed that late TNM stage (HR = 2.93, 95% CI: 1.37-6.27), no PNC (HR = 2.18, 95% CI: 1.08-4.37), history of significant weight-loss (HR = 2.32, 95% CI: 1.04-5.00) and lower quartile (≤38 pg/ml) of postoperative plasma total ghrelin (HR = 3.74, 95% CI: 1.45-9.63) predicted poor survival of patients. The level of other ghrelins did not show independent prediction of survival. Conclusion: Our findings showed that low level of plasma total ghrelin after the gastrectomy could independently predict poor survival in gastric cancer patients. This emphasizes both prognostic and therapeutic significance of this biomarker in gastric cancer. Citation Format: Saeed Soleyman-Jahi, Kazem Zendehdel, Afshin Abdirad, Amir Afraz Fallah, Sevil Ghasemi, Fatemeh Sadeghi. Prognostic significance of plasma ghrelin in patients with gastric cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3412.