Journal Article

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

Horgan, Paul G, Patel, Meera, Quinn, Jean A, Biankin, Andrew V, Hood, Hannah, Rebus, Selma, McMillan, Donald C, Park, James H, Edwards, Joanne, Chang, David K, Pennel, Kathryn A. F, Roseweir, Antonia K

2022

Overview

BackgroundTo understand the relationship between key non-canonical NF-κB kinase IKK-alpha(α), tumour mutational profile and survival in primary colorectal cancer.MethodsImmunohistochemical 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.ResultsTwo 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.ConclusionsThese 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.

• Publisher: Nature Publishing Group
• Subject: Cancer / Colorectal cancer / Cytoplasm / Gene expression / Golgi apparatus / IKK protein / Immunofluorescence / Immunohistochemistry / Multivariate analysis / NF-κB protein / Tumors