Co-ordinated overexpression of SIRT1 and STAT3 is associated with poor survival outcome in gastric cancer patients
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Shu Zhang1,2,*, Shuling Huang1,2,*, Chao Deng1,2,3,*, Yu Cao1,2, Jun Yang4, Guangxia Chen5, Bin Zhang1,2, Chaoqin Duan1,2, Jiong Shi4, Bo Kong1,6, Helmut Friess6, Nanyi Zhao7, Chen Huang8, Xiaoli Huang9, Lei Wang1,2, Xiaoping Zou1,2
1Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China
2Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, China
3Department of Gastroenterology, The People’s Hospital of Kaizhou District, Chongqing, China
4Department of Pathology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China
5Department of Gastroenterology, First People’s Hospital of Xuzhou, Xuzhou, China
6Department of Surgery, Technical University of Munich (TUM), Munich, Germany
7Department of Human Oncology and Pathogenesis, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
8Department of Epidemiology, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China
9Department of Gastroenterology, Nanjing Jiangbei People’s Hospital Affiliated to Southeast University, Nanjing, China
*These authors contributed equally to this work
Xiaoping Zou, email: [email protected]
Lei Wang, email: [email protected]
Keywords: SIRT1, STAT3, gastric cancer, prognosis
Received: October 15, 2016 Accepted: December 15, 2016 Published: January 03, 2017
In many gastric cancer patients, the disease is diagnosed in an advanced stage and therefore the mortality levels are high. Because there is a need to identify novel early diagnostic and prognostic biomarkers, we tested whether SIRT1 and STAT3 are good candidates. Towards this, we used patient tissues representing different stages of gastric cancer including gastric pre-cancerous lesions, early gastric cancer, and advanced gastric cancer, and probed SIRT1, STAT3 and phosphorylated STAT3 (pSTAT3) levels using immunohistochemistry. Our results revealed upregulated expression of SIRT1 in all stages of gastric cancer compared with noncancerous gastric mucosa, suggesting that high SIRT1 levels are likely involved in establishing gastric neoplasticity. However, STAT3 and pSTAT3 levels remained low until the gastric mucosa reached the tumor stage. Moreover, co-ordinated high expression of SIRT1 and STAT3 predicted poor overall survival for advanced gastric cancer patients. In addition, through analysis of gastric cancer patients from the TCGA dataset, we identified SIRT2 as an independent prognostic factor in gastric cancer patients. We postulate that SIRT1 and STAT3 are potential early diagnostic and prognostic markers of gastric cancer. Our study also shows that SIRT1 acts a gatekeeper during gastric tumorigenesis.
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