4.7 Article

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

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BRITISH JOURNAL OF CANCER
卷 126, 期 12, 页码 1704-1714

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DOI: 10.1038/s41416-022-01729-2

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  1. NHS Greater Glasgow & Clyde Endowment Grant
  2. MRC Fellowship [MR/R502327/1]

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Spatial expression of IKK alpha could serve as a potential biomarker in colorectal cancer, with its association with different mutational profiles highlighting possible distinct signaling roles for IKK alpha in the context of colorectal cancer.
BACKGROUND: To understand the relationship between key non-canonical NF-kappa B kinase IKK-alpha(alpha), tumour mutational profile and survival in primary colorectal cancer. METHODS: Immunohistochemical expression of IKK alpha 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 IKK alpha expression. RESULTS: Two patterns of IKK alpha expression were observed; firstly, in the tumour cell cytoplasm and secondly as discrete 'punctate' areas in a juxtanuclear position. Although cytoplasmic expression of IKK alpha was not associated with survival, high 'punctate' IKK alpha expression was associated with significantly reduced cancer-specific survival on multivariate analysis. High punctate expression of IKK alpha was associated with mutations in KRAS and PDGFRA. Dual immunofluorescence suggested punctate IKK alpha expression was co-located with the Golgi apparatus. CONCLUSIONS: These results suggest the spatial expression of IKK alpha is a potential biomarker in colorectal cancer. This is associated with a differential mutational profile highlighting possible distinct signalling roles for IKK alpha in the context of colorectal cancer as well as potential implications for future treatment strategies using IKK alpha inhibitors.

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