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Sulfatase-2: a prognostic biomarker and candidate therapeutic target in patients with pancreatic ductal adenocarcinoma

Lookup NU author(s): Dr Sari Alhasan, Dr Beate Haugk, Laura Ogle, Dr Gary Beale, Anna Long, Professor Alastair Burt, Dr Dina Tiniakos Tiniakos, Dr Despina Televantou, Dr Fareeda Coxon, Professor Herbie Newell, Richard Charnley, Professor Helen Reeves

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Abstract

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.


Publication metadata

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

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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