title: Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer.
abstract: BACKGROUND
  Adiponectin is inversely related to BMI, positively correlates with insulin sensitivity, and has anti-atherogenic 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 receptors--AdipoR1 and AdipoR2--and attempted to correlate their expression with prognosis in gastric cancer patients. AdipoR1 and AdipoR2 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 examined in vitro. Serum adiponectin levels were evaluated in 100 gastric cancer patients, and the expression of AdipoR1 and AdipoR2 was assessed by immunohistochemical staining.
  
  
  RESULTS
  MKN45 and NUGC3 expressed higher levels of AdipoR1 compared to NUGC4, even though there was no significance in AdipoR2 expression. The antiproliferative effect of adiponectin was confirmed in MKN45 and NUGC3 at 10 μg/ml. No significant associations were observed between serum adiponectin levels and clinicopathological characteristics, but lymphatic metastasis and peritoneal dissemination were significantly higher in the negative AdipoR1 immunostaining group (24/32, p = 0.013 and 9/32, p = 0.042, respectively) compared to the positive AdipoR1 group (lymphatic metastasis, 33/68; peritoneal dissemination, 8/68). On the other hand, AdipoR2 expression was only associated with histopathological type (p = 0.001). In survival analysis, the AdipoR1 positive staining group had significantly longer survival rates than the negative staining group (p = 0.01). However, multivariate analysis indicated that AdipoR1 was not an independent prognostic factor on patient's survival on gastric cancer.
  
  
  CONCLUSIONS
  In gastric cancer, adiponectin has the possibility to be involved in cell growth suppression via AdipoR1. The presence of AdipoR1 could be a novel anticancer therapeutic target in gastric cancer.
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan. tkd_tmy@nifty.com
authors.forename: Tomoya
authors.initials: T
authors.lastname: Tsukada
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.forename: Shinichi
authors.initials: S
authors.lastname: Harada
authors.forename: Shiroh
authors.initials: S
authors.lastname: Terai
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Yagi
authors.forename: Jun
authors.initials: J
authors.lastname: Kinoshita
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Oyama
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Tajima
authors.forename: Hideto
authors.initials: H
authors.lastname: Fujita
authors.forename: Itasu
authors.initials: I
authors.lastname: Ninomiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujimura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000494:pharmacology; D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D054419:Receptors, Adiponectin / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D054419:Receptors, Adiponectin
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