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Lookup NU author(s): Dr Sari Alhasan, Dr Beate Haugk, Laura Ogle, Dr Gary Beale, Anna Long, Professor Alastair BurtORCiD, Dr Dina Tiniakos, Dr Despina Televantou, Dr Fareeda Coxon, Professor Herbie Newell, Richard Charnley, Professor Helen ReevesORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0).
Background: 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.Methods: 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.Results: 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 450% 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.Conclusions: 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.
Author(s): Alhasan SF, Haugk B, Ogle LF, Beale GS, Long A, Burt AD, Tiniakos D, Televantou D, Coxon F, Newell DR, Charnley R, Reeves HL
Publication type: Article
Publication status: Published
Journal: British Journal of Cancer
Year: 2016
Volume: 115
Issue: 7
Pages: 797-804
Print publication date: 01/09/2016
Online publication date: 25/08/2016
Acceptance date: 28/07/2016
Date deposited: 09/12/2016
ISSN (print): 0007-0920
ISSN (electronic): 1532-1827
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/bjc.2016.264
DOI: 10.1038/bjc.2016.264
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