The association between markers of tumour cell metabolism, the tumour microenvironment and outcomes in patients with colorectal cancer

Roseweir, A. K. , Clark, J., McSorley, S. T. , vanWyk, H. C. , Quinn, J. A. , Horgan, P. G. , McMillan, D. C. , Park, J. H. and Edwards, J. (2019) The association between markers of tumour cell metabolism, the tumour microenvironment and outcomes in patients with colorectal cancer. International Journal of Cancer, 144(9), pp. 2320-2329. (doi:10.1002/ijc.32045) (PMID:30521130)

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Abstract

Tumour cell anaerobic metabolism has been reported to be a prognostic factor in colorectal cancer. The present study investigated the association between monocarboxylate transporter (MCT) 1, MCT 2, lactate dehydrogenase (LDH) 1 and LDH 5, the tumour microenvironment, and outcome in patients with colorectal cancer. A cohort of 150 patients with stage I‐III CRC were utilised to assess tumour cell expression of MCT‐1, MCT‐2, LDH‐1 and LDH‐5 by immunohistochemistry. Expression levels were dichotomised and associations with tumour factors, the tumour microenvironment and survival analysed. Nuclear LDH‐5 associates with poor prognosis (HR 1.68 95% CI 0.99–2.84, p = 0.050) and trends toward increased tumour stroma percentage (TSP, p = 0.125). Cytoplasmic MCT‐2 also trends toward increased TSP (p = 0.081). When combined into a single score; nuclear LDH‐5 + TSP significantly associated with decreased survival independent of stage (HR 2.61 95% CI 1.27–5.35, p = 0.009), increased tumour budding (p = 0.002) and decreased stromal T‐lymphocytes (p = 0.014). Similarly, cytoplasmic MCT‐2 + TSP significantly associated with decreased survival (HR 2.32 95% CI 1.31–4.11, p = 0.003), decreased necrosis (p = 0.039), and increased tumour budding (p = 0.004). The present study reports that the combination of TSP and nuclear LDH‐5 was significantly associated with survival, increased tumour budding, and decreased stromal T‐lymphocytes. This supports the hypothesis that increased stromal invasion promotes tumour progression via modulation of tumour metabolism. Moreover, MCT‐2 and LDH‐5 may provide promising therapeutic targets for patients with stromal‐rich CRC.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Park, Mr James and Horgan, Professor Paul and Roseweir, Dr Antonia and Clark, Dr Jennifer and McSorley, Dr Stephen and Quinn, Dr Jean and Edwards, Professor Joanne and McMillan, Professor Donald and Van Wyk, Dr Hester
Authors: Roseweir, A. K., Clark, J., McSorley, S. T., vanWyk, H. C., Quinn, J. A., Horgan, P. G., McMillan, D. C., Park, J. H., and Edwards, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:International Journal of Cancer
Publisher:Wiley
ISSN:0020-7136
ISSN (Online):1097-0215
Published Online:06 December 2018
Copyright Holders:Copyright © 2018 UICC
First Published:First published in International Journal of Cancer 144(9):2320-2329
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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