Glucose Transporter 1 Expression as a Marker of Prognosis in Oesophageal Adenocarcinoma

Jaine K. Blayney; Lauren Cairns; Gerald Li; Niamh McCabe; Leanne Stevenson; Christopher J. Peters; Nathan B. Reid; Veronica J. Spence; Chintapuza Chisambo; Damian McManus; Jacqueline James; Stephen McQuaid; Stephanie Craig; Kenneth Arthur; Darragh McArt; Chin-Ann J. Ong; Pierre Lao-Sirieix; Peter Hamilton; Manuel Salto-Tellez; Martin Eatock; Helen G. Coleman; Rebecca C. Fitzgerald; Richard D. Kennedy; Richard C. Turkington

doi:10.18632/oncotarget.24906

Glucose Transporter 1 Expression as a Marker of Prognosis in Oesophageal Adenocarcinoma

Jaine K. Blayney, Lauren Cairns, Gerald Li, Niamh McCabe, Leanne Stevenson, Christopher J. Peters, Nathan B. Reid, Veronica J. Spence, Chintapuza Chisambo, Damian McManus, Jacqueline James, Stephen McQuaid, Stephanie Craig, Kenneth Arthur, Darragh McArt, Chin-Ann J. Ong, Pierre Lao-Sirieix, Peter Hamilton, Manuel Salto-Tellez, Martin EatockHelen G. Coleman, Rebecca C. Fitzgerald, Richard D. Kennedy, Richard C. Turkington

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Abstract

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.
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.
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.
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.

Original language	English
Journal	Oncotarget
Early online date	06 Apr 2018
DOIs	https://doi.org/10.18632/oncotarget.24906
Publication status	Early online date - 06 Apr 2018

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10.18632/oncotarget.24906Licence: CC BY

Glucose transporter 1 expression as a marker of prognosis in oesophageal adenocarcinoma
Copyright 2018 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 2.7 MBLicence: CC BY

Jaine Blayney
- J.Blayneyqub.acuk
- School of Medicine, Dentistry and Biomedical Sciences - Lecturer
- Patrick G Johnston Centre for Cancer Research
Person: Academic
Richard Turkington
- R.Turkingtonqub.acuk
- School of Medicine, Dentistry and Biomedical Sciences - Clinical Reader
- Patrick G Johnston Centre for Cancer Research
Person: Academic

Cite this

Blayney, J. K., Cairns, L., Li, G., McCabe, N., Stevenson, L., Peters, C. J., Reid, N. B., Spence, V. J., Chisambo, C., McManus, D., James, J., McQuaid, S., Craig, S., Arthur, K., McArt, D., Ong, C-A. J., Lao-Sirieix, P., Hamilton, P., Salto-Tellez, M., ... Turkington, R. C. (2018). Glucose Transporter 1 Expression as a Marker of Prognosis in Oesophageal Adenocarcinoma. Oncotarget. https://doi.org/10.18632/oncotarget.24906

@article{8460b1254ac748a49375e9fc8eada01c,

title = "Glucose Transporter 1 Expression as a Marker of Prognosis in Oesophageal Adenocarcinoma",

abstract = "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.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.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.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.",

author = "Blayney, {Jaine K.} and Lauren Cairns and Gerald Li and Niamh McCabe and Leanne Stevenson and Peters, {Christopher J.} and Reid, {Nathan B.} and Spence, {Veronica J.} and Chintapuza Chisambo and Damian McManus and Jacqueline James and Stephen McQuaid and Stephanie Craig and Kenneth Arthur and Darragh McArt and Ong, {Chin-Ann J.} and Pierre Lao-Sirieix and Peter Hamilton and Manuel Salto-Tellez and Martin Eatock and Coleman, {Helen G.} and Fitzgerald, {Rebecca C.} and Kennedy, {Richard D.} and Turkington, {Richard C.}",

year = "2018",

month = apr,

day = "6",

doi = "10.18632/oncotarget.24906",

language = "English",

journal = "Oncotarget",

issn = "1949-2553",

publisher = "Impact Journals",

}

Blayney, JK , Cairns, L, Li, G, McCabe, N, Stevenson, L, Peters, CJ, Reid, NB, Spence, VJ, Chisambo, C, McManus, D , James, J, McQuaid, S, Craig, S, Arthur, K, McArt, D, Ong, C-AJ, Lao-Sirieix, P, Hamilton, P, Salto-Tellez, M, Eatock, M, Coleman, HG, Fitzgerald, RC, Kennedy, RD & Turkington, RC 2018, 'Glucose Transporter 1 Expression as a Marker of Prognosis in Oesophageal Adenocarcinoma', Oncotarget. https://doi.org/10.18632/oncotarget.24906

TY - JOUR

T1 - Glucose Transporter 1 Expression as a Marker of Prognosis in Oesophageal Adenocarcinoma

AU - Blayney, Jaine K.

AU - Cairns, Lauren

AU - Li, Gerald

AU - McCabe, Niamh

AU - Stevenson, Leanne

AU - Peters, Christopher J.

AU - Reid, Nathan B.

AU - Spence, Veronica J.

AU - Chisambo, Chintapuza

AU - McManus, Damian

AU - James, Jacqueline

AU - McQuaid, Stephen

AU - Craig, Stephanie

AU - Arthur, Kenneth

AU - McArt, Darragh

AU - Ong, Chin-Ann J.

AU - Lao-Sirieix, Pierre

AU - Hamilton, Peter

AU - Salto-Tellez, Manuel

AU - Eatock, Martin

AU - Coleman, Helen G.

AU - Fitzgerald, Rebecca C.

AU - Kennedy, Richard D.

AU - Turkington, Richard C.

PY - 2018/4/6

Y1 - 2018/4/6

N2 - 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.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.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.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.

AB - 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.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.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.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.

U2 - 10.18632/oncotarget.24906

DO - 10.18632/oncotarget.24906

M3 - Article

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

ER -

Glucose Transporter 1 Expression as a Marker of Prognosis in Oesophageal Adenocarcinoma

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Jaine Blayney

Richard Turkington

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