Sirtuin-4 (SIRT4) is downregulated and associated with some clinicopathological features in gastric adenocarcinoma.

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. 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. 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). 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.