Circulating tumor cell and oncosome subtypes in portal and peripheral venous circulations may be used for diagnosis and prognostication of pancreatic cancer.

Pancreatic adenocarcinoma remains one of the most devastating cancers, with limited options for early diagnosis and outcome prediction. To address these gaps, we prospectively characterized circulating tumor cells (CTCs) and oncosomes from both the peripheral (PB) and portal vein (PoVB). A total of 121 blood samples from 39 patients (75 PB, 46 PoVB) undergoing endoscopic ultrasound were profiled using multiplex immunofluorescence and computational algorithms for rare event detection. Rare event counts were significantly elevated in pancreatic cancer patients compared to normal donors (p = 4.71e-10). PoVB yielded greater numbers of epithelial and mesenchymal CTCs compared to PB, suggesting restricted systemic entry, while oncosomes were consistently detected in both compartments. Diagnostic accuracy was highest for PB oncosomes and PoVB CTCs. Importantly, PoVB mesenchymal CTCs correlated with 1-year survival (p = 0.0083), and PB oncosomes predicted poor survival (p = 0.0014). These findings highlight complementary diagnostic and prognostic value of PB oncosomes and PoVB CTCs in pancreatic cancer.