UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Decreased serum thrombospondin-1 levels in pancreatic cancer patients up to 24 months prior to clinical diagnosis: Association with diabetes mellitus
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Jenkinson C, Elliott VL, Evans A, Oldfield L, Jenkins RE, O'brien DP, Apostolidou S, Gentry-Maharaj A, Fourkala EO, Jacobs IJ, Menon U, Cox T, Campbell F, Pereira SP, Tuveson DA, Park BK, Greenhalf W, Sutton R, Timms JF, Neoptolemos JP, Costello E
  • Publication date:
    16/11/2015
  • Pagination:
    1734, 1743
  • Journal:
    Clinical Cancer Research
  • Volume:
    22
  • Issue:
    7
  • Status:
    Published
  • Print ISSN:
    1078-0432
Abstract
© 2016 American Association for Cancer Research.Purpose: Identification of serum biomarkers enabling earlier diagnosis of pancreatic ductal adenocarcinoma (PDAC) could improve outcome. Serum protein profiles in patients with preclinical disease and at diagnosis were investigated. Experimental Design: Serum from cases up to 4 years prior to PDAC diagnosis and controls (UKCTOCS, n=174) were studied, alongside samples from patients diagnosed with PDAC, chronic pancreatitis, benign biliary disease, type 2 diabetes mellitus, and healthy subjects (n=298). Isobaric tags for relative and absolute quantification (iTRAQ) enabled comparisons of pooled serum from a test set (n=150). Validation was undertaken using multiple reaction monitoring (MRM) and/or Western blotting in all 472 human samples and samples from a KPC mouse model. Results: iTRAQ identified thrombospondin-1 (TSP-1) as reduced preclinically and in diagnosed samples. MRM confirmed significant reduction in levels of TSP-1 up to 24 months prior to diagnosis. A combination of TSP-1 and CA19-9 gave an AUC of 0.86, significantly outperforming both markers alone (0.69 and 0.77, respectively; P < 0.01). TSP-1 was also decreased in PDAC patients compared with healthy controls (P < 0.05) and patients with benign biliary obstruction (P < 0.01). Low levels of TSP-1 correlated with poorer survival, preclinically (P < 0.05) and at clinical diagnosis (P < 0.02). In PDAC patients, reduced TSP-1 levels were more frequently observed in those with confirmed diabetes mellitus (P < 0.01). Significantly lower levels were also observed in PDAC patients with diabetes compared with individuals with type 2 diabetes mellitus (P=0.01). Conclusions: Circulating TSP-1 levels decrease up to 24 months prior to diagnosis of PDAC and significantly enhance the diagnostic performance of CA19-9. The influence of diabetes mellitus on biomarker behavior should be considered in future studies.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
MRC Clinical Trials Unit at UCL
Author
MRC Clinical Trials Unit at UCL
Author
MRC Clinical Trials Unit at UCL
Author
Inst for Liver and Digestive Hlth
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by