Glucose transporter 1 expression as a marker of prognosis in oesophageal adenocarcinoma
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Jaine K. Blayney1,*, Lauren Cairns1,*, Gerald Li1, Niamh McCabe1, Leanne Stevenson1, Christopher J. Peters2, Nathan B. Reid1, Veronica J. Spence1, Chintapuza Chisambo1, Damian McManus3, Jacqueline James3, Stephen McQuaid3, Stephanie Craig3, Kenneth Arthur3, Darragh McArt1, Chin-Ann J. Ong4, Pierre Lao-Sirieix4, Peter Hamilton1, Manuel Salto-Tellez3, Martin Eatock5, Helen G. Coleman6, Rebecca C. Fitzgerald4, Richard D. Kennedy1, Richard C. Turkington1, On behalf of the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Study Group
1Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, Northern Ireland, UK
2Department of Surgery and Cancer, Imperial College, London, UK
3Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, Northern Ireland, UK
4Hutchison/MRC Cancer Unit, University of Cambridge, Cambridge, UK
5Northern Ireland Cancer Centre, Belfast City Hospital, Lisburn Road, Belfast, Northern Ireland, UK
6Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland, UK
*These authors have contributed equally to this work
Richard C. Turkington, email: firstname.lastname@example.org
Keywords: oesophageal cancer; glucose transporter 1; hypoxia; prognostic; biomarker
Received: December 19, 2017 Accepted: March 09, 2018 Published: April 06, 2018
Background: The current TNM staging system for oesophageal adenocarcinoma (OAC) has limited ability to stratify patients and inform clinical management following neo-adjuvant chemotherapy and surgery.
Results: Functional genomic analysis of the gene expression data using Gene Set Enrichment Analysis (GSEA) identified GLUT1 as putative prognostic marker in OAC.
In the discovery cohort GLUT1 positivity was observed in 114 patients (80.9%) and was associated with poor overall survival (HR 2.08, 95% CI 1.1-3.94; p=0.024) following multivariate analysis. A prognostic model incorporating GLUT1, CRM and nodal status stratified patients into good, intermediate and poor prognosis groups (p< 0.001) with a median overall survival of 16.6 months in the poorest group.
In the validation set 182 patients (69.5%) were GLUT1 positive and the prognostic model separated patients treated with neo-adjuvant chemotherapy and surgery (p<0.001) and surgery alone (p<0.001) into three prognostic groups.
Patients and Methods: Transcriptional profiling of 60 formalin fixed paraffin-embedded (FFPE) biopsies was performed. GLUT1 immunohistochemical staining was assessed in a discovery cohort of 141 FFPE OAC samples treated with neo-adjuvant chemotherapy and surgery at the Northern Ireland Cancer Centre from 2004-2012. Validation was performed in 262 oesophageal adenocarcinomas collected at four OCCAMS consortium centres. The relationship between GLUT1 staining, T stage, N stage, lymphovascular invasion and circumferential resection margin (CRM) status was assessed and a prognostic model developed using Cox Proportional Hazards.
Conclusions: GLUT1 staining combined with CRM and nodal status identifies a poor prognosis sub-group of OAC patients and is a novel prognostic marker following potentially curative surgical resection.
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