Experimental and clinical rsearch of adiponectin receptor expression is associated with good prognosis in gastric cancer

Abstract

Objective Background:Adiponectin is inversely related to body mass index( BMI),positively correlates with insulin sensitivity,and has antiatherogenic effects.In recent years,adiponectin has been well studied in the field of oncology.Adiponectin has been shown to have antiproliferative effects on gastric cancer,and adiponectin expression is inversely correlated with clinical staging of the disease.However,no studies have reported the correlation between serum adiponectin and receptor expression with disease progression.Methods In this study,we evaluated expression levels of 2 adiponectin receptorsAdipo R1 and Adipo R2-and attempted to correlate their expression with prognosis in gastric cancer patients.Adipo R1 and Adipo R2 expression in gastric cancer cell lines ( MKN45,TMK-1,NUGC3,and NUGC4) was evaluated by Western blotting analysis,and the antiproliferative potential of adiponectin was examinedin vitro.Serum adiponectin levels were evaluated in 100 gastric cancer patients,and the expression of Adipo R1 and Adipo R2 was assessed by immunohistochemical staining.Results MKN45 and NUGC3 expressed higher levels of Adipo R1 compared to NUGC4,even though there was no significance in Adipo R2 expression.The antiproliferative effect of adiponectin was confirmed in MKN45 and NUCC3 at 10 mg/L.No significant associations were observed between serum adiponectin levels and clinicopathological characteristics,but lymphatic metastasis and peritoneal dissemination were significantly higher in the negative Adipo R1 immunostaining group ( 24/32,P ＜ 0.05 and 9/32,P ＜ 0.05,respectively) compared to the positive Adipo R1 group (lymphatic metastasis,33/68; peritoneal dissemination,8/68).On the other hand,Adipo R2 expression was only associated with histopathological type (P ＜0.01 ).In survival analysis,the Adipo R1 positive staining group had significantly longer survival rates than the negative staining group (P ＜ 0.05 ).However,multivariate analysis indicated that Adipo R1 was not an independent prognostic factor on patient' s survival on gastric cancer.Conclusion In gastric cancer,adiponectin has the possibility to be involved in cell growth suppression via Adipo R1. Key words: Adiponectin; Adiponectin receptor 1 ; Adiponectin receptor 2 ; Gastric cancer; Survival rate