Keratin 19 as a prognostic marker and contributing factor of metastasis and chemoresistance in high-grade serous ovarian cancer.

Abstract

High-grade serous ovarian cancer (HGSOC) is the most prevalent and lethal subtype of epithelial ovarian cancer (EOC), characterised by extensive peritoneal metastasis. The intermediate filament keratin 19 (KRT19) has been linked to tumour progression and chemoresistance in various cancers. However, its role varies across tumour types and remains unclear for HGSOC. We evaluated KRT19 protein expression in 199 HGSOC patients and correlated findings with clinical outcomes. In vitro, we assessed the effects of KRT19 on tumour-associated mechanisms, including proliferation, migration, adhesion, and spheroid formation. A xenograft mouse model was used to assess tumour burden in vivo. Publicly available datasets enabled in silico validation. KRT19 was significantly overexpressed in HGSOC, and high expression was associated with reduced overall survival. In vivo, KRT19-overexpression increased peritoneal tumour burden. In vitro and ex vivo, KRT19 induced a hybrid epithelial phenotype through enhanced epithelial-mesenchymal plasticity (EMP), promoting adhesion, migration, and spheroid integrity, thereby potentially supporting metastatic processes. Further, KRT19 could contribute to paclitaxel resistance. Altogether, KRT19 represents a potential independent prognostic marker and therapeutic target to inhibit metastatic dissemination.