Exosomal ALPPL2 and THBS2 as biomarkers for early detection and disease monitoring of pancreatic ductal adenocarcinoma.

Background: Lack of reliable biomarkers for early detection and monitoring contributes to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC), as the current clinical marker, CA19-9, lacks adequate specificity and sensitivity.

Methods: Serum concentrations of ALPPL2-positive and THBS2-positive exosomes were measured using an ExoView assay in two cohorts: a cohort of 219 subjects, including non-disease controls and patients with early- or late-stage PDAC, and a longitudinal cohort of 26 patients with advanced PDAC undergoing treatment.

Results: Exosomal ALPPL2 and THBS2 distinguished non-cancer cases from PDAC with high accuracy; area under the curve (AUC) values = 0.983, 0.993, and 0.983 for ALPPL2, THBS2, and the dual marker combination, respectively. Additionally, changes in the concentrations of ALPPL2 and THBS2 exosomes strongly correlated with radiographic tumor size changes during treatment in both CA19-9-elevated (p = 0.016 and 0.014 for ALPPL2 and THBS2, respectively) and non-elevated patients (p = 0.003 and 0.006 for ALPPL2 and THBS2, respectively).

Conclusions: Serum exosomal ALPPL2 and THBS2 can accurately discriminate patients with PDAC from individuals with non-cancerous conditions and healthy controls. Changes in serum exosomal ALPPL2 and THBS2 levels significantly correlate with patients' response to treatment in both CA19-9-elevated and non-elevated patients.