Kallikrein-Related Peptidase 5 Is Associated with Tumor Progression, KRT19 Expression, and Distinct Molecular Programs in High-Grade Serous Ovarian Cancer

Background/Objectives: High-grade serous ovarian cancer (HGSOC) is characterized by peritoneal dissemination and ascites formation. Kallikrein-related peptidase 5 (KLK5) has been linked to aggressive disease. Building on evidence linking KLK4–7 to keratin 19 (KRT19), we hypothesized that a KLK5–KRT19 axis contributes to tumor progression and investigated this potential axis alongside broader KLK5-associated tumor-cell, metabolic, signaling, and microenvironmental mechanisms.

Methods

KLK5-overexpressing ovarian cancer models were characterized using functional assays (adhesion, migration, spheroid formation), KRT19 expression analysis, proteomics, and gene set enrichment analysis. The putative KRT19–KLK5 axis was further investigated in vivo, in silico, and by immunohistochemistry. KLK5-dependent tumor progression was assessed in vivo, including survival and ascites formation, with quantification of CXCL9 in ascitic fluid. Clinical relevance was evaluated by immunohistochemistry in an HGSOC cohort.