Keratin 24 Predicts Poor Prognosis in Breast Cancer.

INTRODUCTION: Keratin (KRT) 24 is a cytoskeletal protein that plays a major role in the formation of intermediate filaments to provide mechanical stability. KRT24 overexpression facilitates tumour cell migration, invasion, and metastasis in several types of cancers. This study evaluates the clinicopathological significance of KRT24 expression in large breast cancer (BC) cohorts with long-term follow-up. METHODS: KRT24 mRNA expression was assessed in publicly available BC datasets (n = 13,025). KRT24 protein expression was evaluated immunohistochemically using well-characterised operable BC cohort (n = 832), and associations with clinicopathological features and patients' outcomes were evaluated. RESULTS: The KRT24 expression, at both transcriptomic and protein levels, was associated with features indicative of poor prognosis, including high histological grade, ER negativity, and HER2 positivity, and with poor patient outcomes. High KRT24 protein expression in chemotherapy-treated patients was significantly correlated with a shorter survival, a higher risk of distant metastases, and BC-related deaths. Additionally, patients with high KRT24 mRNA expression exhibited dysregulation of several differentially expressed genes and enriched pathways, including the cytokine-cytokine receptor interaction pathway, IL-17 signalling pathway, and oestrogen signalling pathway. CONCLUSION: KRT24 expression is associated with poor prognosis in BC. It also plays a predictive role in advanced BC and may represent a potential therapeutic target for patients with this aggressive disease.