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A predictive analysis of the SP120 and 10D7G2 antibodies for human equilibrative nucleoside transporter 1 (hENT1) in pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine

Expression of human equilibrative nucleoside transporter 1 (hENT1) in pancreatic ductal adenocarcinoma (PDAC) has been postulated to be a marker of sensitivity to gemcitabine. However, heterogeneity in the studies attempting to quantify hENT1 expression in patients with PDAC treated with gemcitabine...

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Autores principales: Kalloger, Steve E, Riazy, Maziar, Tessier‐Cloutier, Basile, Karasinska, Joanna M, Gao, Dongxia, Peixoto, Renata D, Samimi, Setareh, Chow, Christine, Wong, Hui‐Li, Mackey, John R, Renouf, Daniel J, Schaeffer, David F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527321/
https://www.ncbi.nlm.nih.gov/pubmed/28770102
http://dx.doi.org/10.1002/cjp2.75
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author Kalloger, Steve E
Riazy, Maziar
Tessier‐Cloutier, Basile
Karasinska, Joanna M
Gao, Dongxia
Peixoto, Renata D
Samimi, Setareh
Chow, Christine
Wong, Hui‐Li
Mackey, John R
Renouf, Daniel J
Schaeffer, David F
author_facet Kalloger, Steve E
Riazy, Maziar
Tessier‐Cloutier, Basile
Karasinska, Joanna M
Gao, Dongxia
Peixoto, Renata D
Samimi, Setareh
Chow, Christine
Wong, Hui‐Li
Mackey, John R
Renouf, Daniel J
Schaeffer, David F
author_sort Kalloger, Steve E
collection PubMed
description Expression of human equilibrative nucleoside transporter 1 (hENT1) in pancreatic ductal adenocarcinoma (PDAC) has been postulated to be a marker of sensitivity to gemcitabine. However, heterogeneity in the studies attempting to quantify hENT1 expression in patients with PDAC treated with gemcitabine has yielded inconclusive results that impede the adoption of hENT1 expression as a predictive biomarker. Tissue microarrays consisting of PDAC specimens from 227 patients acquired between 1987 and 2013 annotated with treatment and outcome information were subjected to staining with two antibodies for hENT1 (10D7G2 and SP120) on a single automated platform and scored by two independent pathologists blinded to treatment and outcome. The resultant scores were subjected to individual predictive disease‐specific survival analysis and to unsupervised hierarchical clustering to generate a multi‐marker classification. Tumour cell staining prevalence using either SP120 or 10D7G2 was predictive of gemcitabine sensitivity (p = 0.02; p = 0.01). When combined, three groups emerged, classified as SP120(Low)_10D7G2(Low), SP120(Low)_10D7G2(High), and SP120(High)_10D7G2(High), in which adjuvant gemcitabine conferred median survival differences of 0.2, 0.8, and 1.5 (p = 0.76, p = 0.06, p = 0.01) years, respectively. These results were largely replicated in multivariable analysis with the P value for the SP120(Low)_10D7G2(High) cluster achieving statistical significance (p = 0.03). These data suggest that either antibody for hENT1 can be used to predict gemcitabine sensitivity in resected PDAC. However, using both antibodies adds valuable information that enables the stratification of patients who can expect to have a good, intermediate, and poor response to adjuvant gemcitabine.
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spelling pubmed-55273212017-08-02 A predictive analysis of the SP120 and 10D7G2 antibodies for human equilibrative nucleoside transporter 1 (hENT1) in pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine Kalloger, Steve E Riazy, Maziar Tessier‐Cloutier, Basile Karasinska, Joanna M Gao, Dongxia Peixoto, Renata D Samimi, Setareh Chow, Christine Wong, Hui‐Li Mackey, John R Renouf, Daniel J Schaeffer, David F J Pathol Clin Res Original Articles Expression of human equilibrative nucleoside transporter 1 (hENT1) in pancreatic ductal adenocarcinoma (PDAC) has been postulated to be a marker of sensitivity to gemcitabine. However, heterogeneity in the studies attempting to quantify hENT1 expression in patients with PDAC treated with gemcitabine has yielded inconclusive results that impede the adoption of hENT1 expression as a predictive biomarker. Tissue microarrays consisting of PDAC specimens from 227 patients acquired between 1987 and 2013 annotated with treatment and outcome information were subjected to staining with two antibodies for hENT1 (10D7G2 and SP120) on a single automated platform and scored by two independent pathologists blinded to treatment and outcome. The resultant scores were subjected to individual predictive disease‐specific survival analysis and to unsupervised hierarchical clustering to generate a multi‐marker classification. Tumour cell staining prevalence using either SP120 or 10D7G2 was predictive of gemcitabine sensitivity (p = 0.02; p = 0.01). When combined, three groups emerged, classified as SP120(Low)_10D7G2(Low), SP120(Low)_10D7G2(High), and SP120(High)_10D7G2(High), in which adjuvant gemcitabine conferred median survival differences of 0.2, 0.8, and 1.5 (p = 0.76, p = 0.06, p = 0.01) years, respectively. These results were largely replicated in multivariable analysis with the P value for the SP120(Low)_10D7G2(High) cluster achieving statistical significance (p = 0.03). These data suggest that either antibody for hENT1 can be used to predict gemcitabine sensitivity in resected PDAC. However, using both antibodies adds valuable information that enables the stratification of patients who can expect to have a good, intermediate, and poor response to adjuvant gemcitabine. John Wiley and Sons Inc. 2017-07-19 /pmc/articles/PMC5527321/ /pubmed/28770102 http://dx.doi.org/10.1002/cjp2.75 Text en © 2017 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Kalloger, Steve E
Riazy, Maziar
Tessier‐Cloutier, Basile
Karasinska, Joanna M
Gao, Dongxia
Peixoto, Renata D
Samimi, Setareh
Chow, Christine
Wong, Hui‐Li
Mackey, John R
Renouf, Daniel J
Schaeffer, David F
A predictive analysis of the SP120 and 10D7G2 antibodies for human equilibrative nucleoside transporter 1 (hENT1) in pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine
title A predictive analysis of the SP120 and 10D7G2 antibodies for human equilibrative nucleoside transporter 1 (hENT1) in pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine
title_full A predictive analysis of the SP120 and 10D7G2 antibodies for human equilibrative nucleoside transporter 1 (hENT1) in pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine
title_fullStr A predictive analysis of the SP120 and 10D7G2 antibodies for human equilibrative nucleoside transporter 1 (hENT1) in pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine
title_full_unstemmed A predictive analysis of the SP120 and 10D7G2 antibodies for human equilibrative nucleoside transporter 1 (hENT1) in pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine
title_short A predictive analysis of the SP120 and 10D7G2 antibodies for human equilibrative nucleoside transporter 1 (hENT1) in pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine
title_sort predictive analysis of the sp120 and 10d7g2 antibodies for human equilibrative nucleoside transporter 1 (hent1) in pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527321/
https://www.ncbi.nlm.nih.gov/pubmed/28770102
http://dx.doi.org/10.1002/cjp2.75
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