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Prospective patient stratification into robust cancer‐cell intrinsic subtypes from colorectal cancer biopsies

Colorectal cancer (CRC) biopsies underpin accurate diagnosis, but are also relevant for patient stratification in molecularly‐guided clinical trials. The consensus molecular subtypes (CMSs) and colorectal cancer intrinsic subtypes (CRISs) transcriptional signatures have potential clinical utility fo...

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Autores principales: Alderdice, Matthew, Richman, Susan D, Gollins, Simon, Stewart, James P, Hurt, Chris, Adams, Richard, McCorry, Amy MB, Roddy, Aideen C, Vimalachandran, Dale, Isella, Claudio, Medico, Enzo, Maughan, Tim, McArt, Darragh G, Lawler, Mark, Dunne, Philip D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947827/
https://www.ncbi.nlm.nih.gov/pubmed/29412457
http://dx.doi.org/10.1002/path.5051
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author Alderdice, Matthew
Richman, Susan D
Gollins, Simon
Stewart, James P
Hurt, Chris
Adams, Richard
McCorry, Amy MB
Roddy, Aideen C
Vimalachandran, Dale
Isella, Claudio
Medico, Enzo
Maughan, Tim
McArt, Darragh G
Lawler, Mark
Dunne, Philip D
author_facet Alderdice, Matthew
Richman, Susan D
Gollins, Simon
Stewart, James P
Hurt, Chris
Adams, Richard
McCorry, Amy MB
Roddy, Aideen C
Vimalachandran, Dale
Isella, Claudio
Medico, Enzo
Maughan, Tim
McArt, Darragh G
Lawler, Mark
Dunne, Philip D
author_sort Alderdice, Matthew
collection PubMed
description Colorectal cancer (CRC) biopsies underpin accurate diagnosis, but are also relevant for patient stratification in molecularly‐guided clinical trials. The consensus molecular subtypes (CMSs) and colorectal cancer intrinsic subtypes (CRISs) transcriptional signatures have potential clinical utility for improving prognostic/predictive patient assignment. However, their ability to provide robust classification, particularly in pretreatment biopsies from multiple regions or at different time points, remains untested. In this study, we undertook a comprehensive assessment of the robustness of CRC transcriptional signatures, including CRIS and CMS, using a range of tumour sampling methodologies currently employed in clinical and translational research. These include analyses using (i) laser‐capture microdissected CRC tissue, (ii) eight publically available rectal cancer biopsy data sets (n = 543), (iii) serial biopsies (from AXEBeam trial, NCT00828672; n = 10), (iv) multi‐regional biopsies from colon tumours (n = 29 biopsies, n = 7 tumours), and (v) pretreatment biopsies from the phase II rectal cancer trial COPERNCIUS (NCT01263171; n = 44). Compared to previous results obtained using CRC resection material, we demonstrate that CMS classification in biopsy tissue is significantly less capable of reliably classifying patient subtype (43% unknown in biopsy versus 13% unknown in resections, p = 0.0001). In contrast, there was no significant difference in classification rate between biopsies and resections when using the CRIS classifier. Additionally, we demonstrated that CRIS provides significantly better spatially‐ and temporally‐ robust classification of molecular subtypes in CRC primary tumour tissue compared to CMS (p = 0.003 and p = 0.02, respectively). These findings have potential to inform ongoing biopsy‐based patient stratification in CRC, enabling robust and stable assignment of patients into clinically‐informative arms of prospective multi‐arm, multi‐stage clinical trials. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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spelling pubmed-59478272018-05-17 Prospective patient stratification into robust cancer‐cell intrinsic subtypes from colorectal cancer biopsies Alderdice, Matthew Richman, Susan D Gollins, Simon Stewart, James P Hurt, Chris Adams, Richard McCorry, Amy MB Roddy, Aideen C Vimalachandran, Dale Isella, Claudio Medico, Enzo Maughan, Tim McArt, Darragh G Lawler, Mark Dunne, Philip D J Pathol Original Papers Colorectal cancer (CRC) biopsies underpin accurate diagnosis, but are also relevant for patient stratification in molecularly‐guided clinical trials. The consensus molecular subtypes (CMSs) and colorectal cancer intrinsic subtypes (CRISs) transcriptional signatures have potential clinical utility for improving prognostic/predictive patient assignment. However, their ability to provide robust classification, particularly in pretreatment biopsies from multiple regions or at different time points, remains untested. In this study, we undertook a comprehensive assessment of the robustness of CRC transcriptional signatures, including CRIS and CMS, using a range of tumour sampling methodologies currently employed in clinical and translational research. These include analyses using (i) laser‐capture microdissected CRC tissue, (ii) eight publically available rectal cancer biopsy data sets (n = 543), (iii) serial biopsies (from AXEBeam trial, NCT00828672; n = 10), (iv) multi‐regional biopsies from colon tumours (n = 29 biopsies, n = 7 tumours), and (v) pretreatment biopsies from the phase II rectal cancer trial COPERNCIUS (NCT01263171; n = 44). Compared to previous results obtained using CRC resection material, we demonstrate that CMS classification in biopsy tissue is significantly less capable of reliably classifying patient subtype (43% unknown in biopsy versus 13% unknown in resections, p = 0.0001). In contrast, there was no significant difference in classification rate between biopsies and resections when using the CRIS classifier. Additionally, we demonstrated that CRIS provides significantly better spatially‐ and temporally‐ robust classification of molecular subtypes in CRC primary tumour tissue compared to CMS (p = 0.003 and p = 0.02, respectively). These findings have potential to inform ongoing biopsy‐based patient stratification in CRC, enabling robust and stable assignment of patients into clinically‐informative arms of prospective multi‐arm, multi‐stage clinical trials. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. John Wiley & Sons, Ltd 2018-03-25 2018-05 /pmc/articles/PMC5947827/ /pubmed/29412457 http://dx.doi.org/10.1002/path.5051 Text en © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Papers
Alderdice, Matthew
Richman, Susan D
Gollins, Simon
Stewart, James P
Hurt, Chris
Adams, Richard
McCorry, Amy MB
Roddy, Aideen C
Vimalachandran, Dale
Isella, Claudio
Medico, Enzo
Maughan, Tim
McArt, Darragh G
Lawler, Mark
Dunne, Philip D
Prospective patient stratification into robust cancer‐cell intrinsic subtypes from colorectal cancer biopsies
title Prospective patient stratification into robust cancer‐cell intrinsic subtypes from colorectal cancer biopsies
title_full Prospective patient stratification into robust cancer‐cell intrinsic subtypes from colorectal cancer biopsies
title_fullStr Prospective patient stratification into robust cancer‐cell intrinsic subtypes from colorectal cancer biopsies
title_full_unstemmed Prospective patient stratification into robust cancer‐cell intrinsic subtypes from colorectal cancer biopsies
title_short Prospective patient stratification into robust cancer‐cell intrinsic subtypes from colorectal cancer biopsies
title_sort prospective patient stratification into robust cancer‐cell intrinsic subtypes from colorectal cancer biopsies
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947827/
https://www.ncbi.nlm.nih.gov/pubmed/29412457
http://dx.doi.org/10.1002/path.5051
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