# Threonine and tyrosine kinase (TTK) mRNA and protein expression in breast cancer; prognostic significance in the neoadjuvant setting

## TL;DR

This study explores TTK protein and mRNA levels in breast cancer patients before and after chemotherapy, finding that higher TTK levels are linked to worse survival and suggesting TTK as a potential biomarker and treatment target.

## Contribution

The study is the first to investigate TTK expression in breast cancer patients undergoing neoadjuvant chemotherapy and links it to survival outcomes.

## Key findings

- TTK mRNA expression is significantly elevated in breast cancer tissues compared to normal tissues.
- High TTK mRNA levels are associated with reduced overall survival in breast cancer patients.
- TTK protein expression increases significantly after neoadjuvant chemotherapy and correlates with reduced survival.

## Abstract

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.

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.

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.

This study investigates threonine and tyrosine kinase (TTK) expression in pre‐ and post‐neoadjuvant chemotherapy breast cancer patients. TTK mRNA expression was elevated in breast cancer tissues, predicting reduced survival. Notably, TTK protein expression in neoadjuvant chemotherapy‐treated breast cancer patients was up‐regulated post‐therapy and correlated with reduced survival, highlighting TTK as a breast cancer biomarker and possible therapeutic target.