title: SIRT3 & SIRT7: Potential Novel Biomarkers for Determining Outcome in Pancreatic Cancer Patients.
abstract: OBJECTIVE
  The sirtuin gene family has been linked with tumourigenesis, in both a tumour promoter and suppressor capacity. Information regarding the function of sirtuins in pancreatic cancer is sparse and equivocal. We undertook a novel study investigating SIRT1-7 protein expression in a cohort of pancreatic tumours. The aim of this study was to establish a protein expression profile for SIRT1-7 in pancreatic ductal adenocarcinomas (PDAC) and to determine if there were associations between SIRT1-7 expression, clinico-pathological parameters and patient outcome.
  
  
  METHODS
  Immunohistochemical analysis of SIRT1-7 protein levels was undertaken in a tissue micro-array comprising 77 resected PDACs. Statistical analyses determined if SIRT1-7 protein expression was associated with clinical parameters or outcome.
  
  
  RESULTS
  Two sirtuin family members demonstrated significant associations with clinico-pathological parameters and patient outcome. Low level SIRT3 expression in the tumour cytoplasm correlated with more aggressive tumours, and a shorter time to relapse and death, in the absence of chemotherapeutic intervention. Low levels of nuclear SIRT7 expression were also associated with an aggressive tumour phenotype and poorer outcome, as measured by disease-free and disease-specific survival time, 12 months post-diagnosis.
  
  
  CONCLUSIONS
  Our data suggests that SIRT3 and SIRT7 possess tumour suppressor properties in the context of pancreatic cancer. SIRT3 may also represent a novel predictive biomarker to determine which patients may or may not respond to chemotherapy. This study opens up an interesting avenue of investigation to potentially identify predictive biomarkers and novel therapeutic targets for pancreatic cancer, a disease that has seen no significant improvement in survival over the past 40 years.
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Liane M
authors.initials: LM
authors.lastname: McGlynn
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: McCluney
authors.affiliation: West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom; Academic Department of Surgery, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Nigel B
authors.initials: NB
authors.lastname: Jamieson
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Jackie
authors.initials: J
authors.lastname: Thomson
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Alasdair I
authors.initials: AI
authors.lastname: MacDonald
authors.affiliation: Institute of Cancer Sciences, Pathology, Wolfson Building, Beatson Labs, Glasgow, United Kingdom.
authors.forename: Karin
authors.initials: K
authors.lastname: Oien
authors.affiliation: West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Euan J
authors.initials: EJ
authors.lastname: Dickson
authors.affiliation: West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: C Ross
authors.initials: CR
authors.lastname: Carter
authors.affiliation: West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: McKay
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Shiels
mesh_terms: D000918:Antibody Specificity / Q000276:immunology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D056566:Sirtuin 3 / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C510661:SIRT7 protein, human; C466093:SIRT3 protein, human; D056566:Sirtuin 3; D037761:Sirtuins