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

Automated summary

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.