title: Sirtuin-4 (SIRT4) is downregulated and associated with some clinicopathological features in gastric adenocarcinoma.
abstract: BACKGROUND
  Several members of the SIRT family (SIRT1-7), which are a highly conserved family of NAD(+)-dependent enzymes, play an important role in tumor formation. Recently, several studies have suggested that SIRT4 can regulate glutamine metabolism yet have tumor suppressor function too. However, our understanding of SIRT4 expression and its association with the clinicopathological parameters remains poor.
  
  
  METHODS
  We evaluated SIRT4 protein expression levels in gastric adenocarcinoma and corresponding normal gastric tissue by immunohistochemical staining on a tissue microarray that included 75 gastric adenocarcinoma patients. We also determined the association between SIRT4 expression levels and selected clinicopathological parameters in gastric adenocarcinoma.
  
  
  RESULTS
  We found that the expression level of SIRT4 in gastric adenocarcinoma was significantly lower than the corresponding normal tissue levels (P=0.003). Besides, lower SIRT4 levels were observed in pathological grade (P=0.002), depth of tumor invasion (P=0.034), positive lymph node numbers (P=0.005) and UICC stage (P=0.002).
  
  
  CONCLUSIONS
  Our results support the notion that SIRT4 behaves as a tumor suppressor at the human tissue protein level. In addition, our data indicate that SIRT4 might be closely involved in the process of gastric adenocarcinoma development and it might potentially serve as a diagnostic biomarker and therapeutic target in gastric adenocarcinoma.
authors.affiliation: Department of General Surgery, First People's Hospital, Shanghai Jiao Tong Univerisity, 85 Wujin Road, Shanghai 200080, China.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of General Surgery, First People's Hospital, Shanghai Jiao Tong Univerisity, 85 Wujin Road, Shanghai 200080, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Cui
authors.affiliation: Department of General Surgery, First People's Hospital, Shanghai Jiao Tong Univerisity, 85 Wujin Road, Shanghai 200080, China.
authors.forename: Fudong
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Pathology, First People's Hospital, Shanghai Jiao Tong Univerisity, 85 Wujin Road, Shanghai 200080, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Pathology, First People's Hospital, Shanghai Jiao Tong Univerisity, 85 Wujin Road, Shanghai 200080, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pathology, First People's Hospital, Shanghai Jiao Tong Univerisity, 85 Wujin Road, Shanghai 200080, China.
authors.forename: Huamei
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of General Surgery, First People's Hospital, Shanghai Jiao Tong Univerisity, 85 Wujin Road, Shanghai 200080, China. Electronic address: pengzhp@hotmail.com.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D015536:Down-Regulation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism*; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D024101:Mitochondrial Proteins; C525357:SIRT4 protein, human; D037761:Sirtuins
keywords: Carcinogenesis; Gastric adenocarcinoma; SIRT4