title: Sulfatase-2: a prognostic biomarker and candidate therapeutic target in patients with pancreatic ductal adenocarcinoma.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer death in the UK. Its poor prognosis is attributed to late detection and limited therapeutic options. Expression of SULF2, an endosulfatase that modulates heparan sulfate proteoglycan 6-O-sulfation and is reportedly tumourigenic in different types of cancer, was investigated.
  
  
  
  SULF2 expression was determined immunohistochemically in archival surgical resection tissue sections from 93 patients with a confirmed histological diagnosis of PDAC between 2002 and 2008 followed for a median of 9 years. Relationships with clinico-pathological parameters and patient survival were explored.
  
  
  
  The majority of PDACs showed positive SULF2 staining in tumour cells and intratumoural or tumour-adjacent stroma. Greater than 25% SULF2-positive tumour cells was present in 60% of cancers and correlated with tumour stage (P=0.002) and perineural invasion (P=0.024). SULF2 intensity was scored moderate or strong in 81% of cancers and positively correlated with vascular invasion (P=0.015). High SULF2 expression, defined as >50% SULF2-positive tumour cells and strong SULF2 staining, was associated with shorter time to radiological progression (P=0.018, HR 1.98, CI 1.13-3.47). Similarly, by multivariate analysis, high SULF2 expression was independently associated with poorer survival (P=0.004, HR 2.10, CI 1.26-3.54), with a median survival of 11 months vs 21 months for lower PDAC SULF2.
  
  
  
  Elevated SULF2 in PDAC was associated with advanced tumour stage, vascular invasion, shorter interval to radiological progression and shorter overall survival. SULF2 may have roles as a prognostic biomarker and as a therapeutic target for patients with PDAC.
authors: Northern Institute for Cancer Research, Paul O'Gorman Building, The Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors: Sari F
authors: SF
authors: Alhasan
authors: Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.
authors: Beate
authors: B
authors: Haugk
authors: Northern Institute for Cancer Research, Paul O'Gorman Building, The Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors: Laura F
authors: LF
authors: Ogle
authors: Northern Institute for Cancer Research, Paul O'Gorman Building, The Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors: Gary S
authors: GS
authors: Beale
authors: Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.
authors: Anna
authors: A
authors: Long
authors: Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.|School of Medicine, Eleanor Harrald Building, Frome Road, The University of Adelaide, Adelaide, 5000 South Australia, Australia.
authors: Alastair D
authors: AD
authors: Burt
authors: Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.|Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors: Dina
authors: D
authors: Tiniakos
authors: Northern Institute for Cancer Research, Paul O'Gorman Building, The Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.|Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.
authors: Despina
authors: D
authors: Televantou
authors: Hepatopancreatobiliary multidisciplinary team, Freeman Hospital, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK.
authors: Fareeda
authors: F
authors: Coxon
authors: Northern Institute for Cancer Research, Paul O'Gorman Building, The Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors: David R
authors: DR
authors: Newell
authors: Hepatopancreatobiliary multidisciplinary team, Freeman Hospital, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK.
authors: Richard
authors: R
authors: Charnley
authors: Northern Institute for Cancer Research, Paul O'Gorman Building, The Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.|Hepatopancreatobiliary multidisciplinary team, Freeman Hospital, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK.
authors: Helen L
authors: HL
authors: Reeves
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality / Q000601:surgery; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis*; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality / Q000601:surgery; D010865:Pilot Projects; D011379:Prognosis; D012189:Retrospective Studies; D013429:Sulfatases; D015238:Sulfotransferases / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D015238:Sulfotransferases; C470792:SULF2 protein, human; D013429:Sulfatases