Differential Associations of PIVKA-II with Epithelial and Mesenchymal Features in HCC and PDAC

Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are aggressivemalignancies characterized by a poor prognosis and resistance to conventionaltherapies. Mounting evidence suggests the pivotal role of epithelial–mesenchymal transition(EMT) in tumor progression, metastasis, and therapeutic resistance in these cancers.Protein induced by vitamin K absence II (PIVKA-II)—a valuable HCC detector—has ultimatelyemerged as a potentially relevant biomarker in PDAC, serving as both a serumbiomarker and a prognostic indicator. This study investigates the putative link betweenPIVKA-II expression and the EMT process in HCC and PDAC. Using a Western blot analysisand electrochemiluminescence immunoassay (ECLIA), we quantified PIVKA-II serumlevels alongside two canonical EMT markers—Vimentin and E-cadherin—in selected cohorts.Emerging data suggest a dual, context-dependent role for PIVKA-II. Beyond itsdiagnostic value in both malignancies, its co-expression with EMT markers points to a potentialmechanistic involvement in tumor invasiveness and phenotypic plasticity. Notably,the selective detection of E-cadherin in HCC implies limited EMT activation and a preservationof the epithelial phenotype, whereas the higher expression of Vimentin in PDACreflects a more substantial shift toward EMT. We provide a comprehensive analysis of keymolecular markers, their involvement in EMT-driven pathophysiological mechanisms, andtheir potential as novel diagnostic tools.