Alderdice, M, Richman, SD orcid.org/0000-0003-3993-5041, Gollins, S et al. (12 more authors) (2018) Prospective patient stratification into robust cancer‐cell intrinsic subtypes from colorectal cancer biopsies. Journal of Pathology, 245 (1). pp. 19-28. ISSN 0022-3417
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 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 Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
Keywords: | colorectal cancer; gene expression profiling; molecular stratification; biopsy; transcriptional signatures; intrinsic subtypes; consensus molecular subtypes |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Pathology & Tumour Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Feb 2018 16:49 |
Last Modified: | 16 May 2018 14:18 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/path.5051 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:127411 |
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