Threonine and tyrosine kinase (TTK) mRNA and protein expression in breast cancer; prognostic significance in the neoadjuvant setting
Ashi, Abrar Awaji, Aeshah A Bond, Jacquelyn Johnson, Colin A Shaaban, Abeer M Bell, Sandra M
Ashi, Abrar
Awaji, Aeshah A
Bond, Jacquelyn
Johnson, Colin A
Shaaban, Abeer M
Bell, Sandra M
Affiliation
University of Leeds; Leeds Teaching Hospitals NHS Trust; University of Birmingham; University Hospitals Birmingham NHS Foundation Trust
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Publication date
2025-01-07
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Abstract
Aims: Threonine and tyrosine kinase (TTK) is up-regulated in triple-negative breast cancer (TNBC), yet its expression in patients undergoing neoadjuvant chemotherapy (NACT) remains unexplored. This investigation aims to assess TTK protein expression in treatment-naïve pre-treatment cores and paired pre- and post-NACT breast cancer (BC) cohorts, as well as its correlation with microcephaly 1 (MCPH1) protein expression.
Methods and results: Transcriptomic data were sourced from the Gene Expression Omnibus microarray database for mRNA expression analysis. TTK protein expression was evaluated using immunohistochemistry staining, employing receiver operating characteristic curve analysis to determine an optimal TTK expression cut-off point. The association between TTK expression, clinicopathological parameters and survival outcomes was examined. Additionally, MCPH1 protein expression was assessed in a pilot study. Analysis revealed a significantly elevated TTK mRNA expression in BC tissue compared to normal breast tissue, with high TTK mRNA levels predicting reduced overall survival. Notably, TTK protein expression increased significantly post-NACT in a paired cohort. Conversely, decreased TTK protein expression pre-NACT was correlated with improved overall survival.
Conclusions: High TTK and low MCPH1 protein expression was significantly correlated, highlighting TTK's potential as a biomarker for BC and a therapeutic target for MCPH1-deficient cancer cells.
Citation
Ashi A, Awaji AA, Bond J, Johnson CA, Shaaban AM, Bell SM. Threonine and tyrosine kinase (TTK) mRNA and protein expression in breast cancer; prognostic significance in the neoadjuvant setting. Histopathology. 2025 May;86(6):916-932. doi: 10.1111/his.15399. Epub 2025 Jan 7.
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Article