title: Evaluation in pre-diagnosis samples discounts  ICAM-1 and TIMP-1 as biomarkers for earlier  diagnosis of pancreatic cancer.
abstract: Circulating intercellular adhesion molecule-1 (ICAM-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have been widely proposed as potential diagnostic biomarkers for pancreatic ductal adenocarcinoma (PDAC). We report on serum protein levels prior to clinical presentation of pancreatic cancer. Serum ICAM-1 and TIMP-1 were measured by ELISA in two case–control sets: 1) samples from patients diagnosed with pancreatic cancer (n = 40), chronic pancreatitis (n = 20), benign jaundice due to gall stones (n = 20) and healthy subjects (n = 20); 2) a preclinical set from the UK Collaborative Trial of Ovarian Cancer Screening biobank of samples collected from 27 post-menopausal women 0–12 months prior to diagnosis of pancreatic cancer and controls matched for date of donation and centre. Levels of ICAM-1 and TIMP-1 were significantly elevated in set 1 in PDAC patients with jaundice compared to PDAC patients without jaundice and both proteins were elevated in patients with jaundice due to gall stones. Neither protein was elevated in samples taken 0–12 months prior to PDAC diagnosis compared to non-cancer control samples. In conclusion, evaluation in pre-diagnosis samples discounts ICAM-1 and TIMP-1 as biomarkers for earlier diagnosis of pancreatic cancer. Failure to account for obstructive jaundice may have contributed to the previous promise of these candidate biomarkers.
  
  
  CONCLUSIONS
  Pancreatic cancer is usually diagnosed when at an advanced stage which greatly limits therapeutic options. Biomarkers that could facilitate earlier diagnosis are urgently sought.
authors.forename: C
authors.initials: C
authors.lastname: Jenkinson
authors.forename: V
authors.initials: V
authors.lastname: Elliott
authors.forename: U
authors.initials: U
authors.lastname: Menon
authors.forename: S
authors.initials: S
authors.lastname: Apostolidou
authors.forename: O E
authors.initials: OE
authors.lastname: Fourkala
authors.forename: A
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.forename: S P
authors.initials: SP
authors.lastname: Pereira
authors.forename: I
authors.initials: I
authors.lastname: Jacobs
authors.forename: T F
authors.initials: TF
authors.lastname: Cox
authors.forename: W
authors.initials: W
authors.lastname: Greenhalf
authors.forename: J F
authors.initials: JF
authors.lastname: Timms
authors.forename: R
authors.initials: R
authors.lastname: Sutton
authors.forename: J P
authors.initials: JP
authors.lastname: Neoptolemos
authors.forename: E
authors.initials: E
authors.lastname: Costello
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; C573420:ICAM1 protein, human; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D018799:Intercellular Adhesion Molecule-1