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)
Text
262704.pdf - Published Version Available under License Creative Commons Attribution. 8MB |
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 Horgan, Professor Paul and Hood, Dr Hannah and Roseweir, Dr Antonia and Pennel, Miss Kathryn and Rebus, Ms Selma and Quinn, Dr Jean and Edwards, Professor Joanne and Chang, Professor David and Biankin, Professor Andrew and Patel, Dr Meera and McMillan, Professor Donald |
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 |
University Staff: Request a correction | Enlighten Editors: Update this record