title: Co-ordinated overexpression of SIRT1 and STAT3 is associated with poor survival outcome in gastric cancer patients.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.|Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.|Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, China.
authors.forename: Shuling
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.|Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, China.|Department of Gastroenterology, The People's Hospital of Kaizhou District, Chongqing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.|Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Pathology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, First People's Hospital of Xuzhou, Xuzhou, China.
authors.forename: Guangxia
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.|Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.|Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, China.
authors.forename: Chaoqin
authors.initials: C
authors.lastname: Duan
authors.affiliation: Department of Pathology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.|Department of Surgery, Technical University of Munich (TUM), Munich, Germany.
authors.forename: Bo
authors.initials: B
authors.lastname: Kong
authors.affiliation: Department of Surgery, Technical University of Munich (TUM), Munich, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.affiliation: Department of Human Oncology and Pathogenesis, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Nanyi
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Epidemiology, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Nanjing Jiangbei People's Hospital Affiliated to Southeast University, Nanjing, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.|Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.|Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D050796:STAT3 Transcription Factor / Q000096:biosynthesis*; D056564:Sirtuin 1 / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: SIRT1; STAT3; gastric cancer; prognosis