Spatial expression of IKK-alpha is associated with a differential mutational landscape and survival in primary colorectal cancer

Patel, M. et al. (2022) Spatial expression of IKK-alpha is associated with a differential mutational landscape and survival in primary colorectal cancer. British Journal of Cancer, 126(12), pp. 1704-1714. (doi: 10.1038/s41416-022-01729-2) (PMID:35173303) (PMCID:PMC9174220)

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Abstract

Background: To understand the relationship between key non-canonical NF-κB kinase IKK-alpha(α), tumour mutational profile and survival in primary colorectal cancer. Methods: Immunohistochemical expression of IKKα was assessed in a cohort of 1030 patients who had undergone surgery for colorectal cancer using immunohistochemistry. Mutational tumour profile was examined using a customised gene panel. Immunofluorescence was used to identify the cellular location of punctate IKKα expression. Results: Two patterns of IKKα expression were observed; firstly, in the tumour cell cytoplasm and secondly as discrete ‘punctate’ areas in a juxtanuclear position. Although cytoplasmic expression of IKKα was not associated with survival, high ‘punctate’ IKKα expression was associated with significantly reduced cancer-specific survival on multivariate analysis. High punctate expression of IKKα was associated with mutations in KRAS and PDGFRA. Dual immunofluorescence suggested punctate IKKα expression was co-located with the Golgi apparatus. Conclusions: These results suggest the spatial expression of IKKα is a potential biomarker in colorectal cancer. This is associated with a differential mutational profile highlighting possible distinct signalling roles for IKKα in the context of colorectal cancer as well as potential implications for future treatment strategies using IKKα inhibitors.

Item Type:Articles
Additional Information:Funding for the Edwards Lab was from the NHS Greater Glasgow & Clyde Endowment Grant to MP and KP was supported by an MRC Fellowship (MR/ R502327/1).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Park, Mr James and Rebus, Ms Selma and Roseweir, Dr Antonia and Pennel, Kathryn and Quinn, Dr Jean and Chang, Professor David and Horgan, Professor Paul and Biankin, Professor Andrew and Patel, Dr Meera and McMillan, Professor Donald and Edwards, Professor Joanne and Hood, Dr Hannah
Authors: Patel, M., Pennel, K. A.F., Quinn, J. A., Hood, H., Chang, D. K., Biankin, A. V., Rebus, S., Roseweir, A. K., Park, J. H., Horgan, P. G., McMillan, D. C., and Edwards, J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:British Journal of Cancer
Publisher:Springer Nature
ISSN:0007-0920
ISSN (Online):1532-1827
Published Online:16 February 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in British Journal of Cancer 126(12): 1704-1714
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
313949National Productivity Investment Fund StudentshipsGeorge BaillieMedical Research Council (MRC)MR/R502327/1MVLS - Graduate School
170634Defining Platinum and PARP Responsive Molecular Phenotypes of Pancreatic Cancer.Andrew BiankinWellcome Trust (WELLCOTR)103721/Z/14/ZInstitute of Cancer Sciences
174160Precision PancAndrew BiankinCancer Research UK (CRUK)C29717/A23526CS -Translational Research Centre
174159Precision-Panc: a dynamic therapeutic development platform for pancreatic cancerDavid ChangCancer Research UK (CRUK)C51058/A25407CS -Translational Research Centre