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

Abstract

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.