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

Alderdice, Matthew, Richman, Susan D, Gollins, Simon, Stewart, Peter, Hurt, Christopher ORCID: https://orcid.org/0000-0003-1206-8355, Adams, Richard ORCID: https://orcid.org/0000-0003-3915-7243, McCorry, Amy, Roddy, Aideen, Vimalachandran, Dale, Isella, Claudio, Medico, Enzo, Maughan, Tim, McArt, Darragh G, Lawler, Mark and Dunne, Philip D 2018. Prospective patient stratification into robust cancer-cell intrinsic subtypes from colorectal cancer biopsies. The Journal of Pathology 245 (1) , pp. 19-28. 10.1002/path.5051

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Abstract

Colorectal cancer (CRC) biopsies underpin accurate diagnosis, but are also relevant for patient stratification in molecularly-guided clinical trials. The consensus molecular subtypes (CMS) and colorectal cancer intrinsic subtypes (CRIS) transcriptional signatures have potential clinical utility for improving prognostic/predictive patient assignment. However, their ability to provide robust classification, particularly in pre-treatment 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) pre-treatment 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Centre for Trials Research (CNTRR) Medicine
Publisher:	Wiley
ISSN:	0022-3417
Funders:	CRUK
Date of First Compliant Deposit:	12 February 2018
Date of Acceptance:	1 February 2018
Last Modified:	15 Nov 2024 16:45
URI:	https://orca.cardiff.ac.uk/id/eprint/109024

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