Transcriptional subtyping and CD8 immunohistochemistry identifies patients with stage II and III colorectal cancer with poor prognosis who benefit from adjuvant chemotherapy

Allen, W. L. et al. (2018) Transcriptional subtyping and CD8 immunohistochemistry identifies patients with stage II and III colorectal cancer with poor prognosis who benefit from adjuvant chemotherapy. JCO Precision Oncology(2), pp. 1-15. (doi: 10.1200/PO.17.00241) (PMID:30088816) (PMCID:PMC6040635)

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Abstract

Purpose Transcriptomic profiling of colorectal cancer (CRC) has led to the identification of four consensus molecular subtypes (CMS1 to 4) that have prognostic value in stage II and III disease. More recently, the Colorectal Cancer Intrinsic Subtypes (CRIS) classification system has helped to define the biology specific to the epithelial component of colorectal tumors; however, the clinical value of these classification systems in the prediction of response to standard-of-care adjuvant chemotherapy remains unknown. Patients and Methods Using samples from four European sites, we assembled a novel cohort of patients with stage II and III CRC (n = 156 samples) and performed transcriptomic profiling and targeted sequencing and generated a tissue microarray to enable integrated multiomics analyses. We also accessed data from two published cohorts of patients with stage II and III CRC: GSE39582 and GSE14333 (n = 479 and n = 185 samples, respectively). Results The epithelial-rich CMS2 subtype of CRC benefitted significantly from treatment with adjuvant chemotherapy in both stage II and III disease (P = .02 and P < .001, respectively), whereas the CMS3 subtype significantly benefitted in stage III only (P = .001). After CRIS substratification of CMS2, we observed that only the CRIS-C subtype significantly benefitted from treatment with adjuvant chemotherapy in stage II and III disease (P = .0081 and P < .001, respectively), whereas the CRIS-D subtype significantly benefitted in stage III only (P = .0034). We also observed that CRIS-C patients with low levels of CD8+ tumor-infiltrating lymphocytes were most at risk for relapse in both stage II and III disease (log-rank P = .0031; hazard ratio, 12.18 [95% CI, 1.51 to 98.58]). Conclusion Patient stratification using a combination of transcriptional subtyping and CD8 immunohistochemistry analyses is capable of identifying patients with poor prognostic stage II and III disease who benefit from adjuvant standard-of-care chemotherapy. These findings are particularly relevant for patients with stage II disease, where the overall benefit of adjuvant chemotherapy is marginal.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilson, Professor Richard
Authors: Allen, W. L., Dunne, P. D., McDade, S., Scanlon, E., Loughrey, M., Coleman, H. G., McCann, C., McLaughlin, K., Nemeth, Z., Syed, N. A., Jithesh, P. V., Arthur, K., Wilson, R., Coyle, V. M., McArt, D., Murray, G. I., Samuel, L., Nuciforo, P., Jimenez, J., Argiles, G., Dienstmann, R., Tabernero, J., Picariello, L., Messerini, L., Nobili, S., Mini, E., Sheahan, K., Ryan, E., Johnston, P. G., Van Schaeybroeck, S., Lawler, M., and Longley, D. B.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:JCO Precision Oncology
Publisher:American Society of Clinical Oncology
ISSN:2473-4284
ISSN (Online):2473-4284
Copyright Holders:© 2018 by American Society of Clinical Oncology
First Published:First published in JCO Precision Oncology 1 Jun 2018
Publisher Policy:Reproduced under a Creative Commons Licence

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