Abstract 2497: Extracellular vesicle based ALPPL2 and THBS2 as biomarkers for disease monitoring in patients with pancreatic ductal adenocarcinoma
Authors: Kuntal Halder, Gayle Jameson, Erkut Borazanci, Wei Lin, Dereck Cridebring, Daniel Von Hoff, Haiyong Han
Journal: Cancer Research (2024)

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains a formidable challenge in the realm of oncology, characterized by its aggressive nature and resistance to treatment. Several therapeutic regimens have been shown to extend patient survival, but the majority of the patients become refractory to the treatments in a short period of time. Hence, it is critical to monitor a patient’s response to treatment in a timely manner so that different treatment regimens can be considered promptly. Currently, CA19-9 is the most common blood-based marker being used to monitor disease burden in patients with PDAC. However, 15-20% of patients with PDAC do not have elevated blood CA19-9 levels. In this study, we sought to determine the utility of two circulating extracellular vesicle (EV) based protein biomarkers, ALPPL2 (Alkaline phosphatase, placental-like 2) and THBS2 (Thrombospondin 2), for disease monitoring in patients with PDAC. We first established and optimized EV assays using the ExoViewTM platform for detecting and quantifying the number of ALPPL2+ or THBS2+ EVs in serum samples. We then determined the concentrations of ALPPL2+ or THBS2+ EVs in samples from healthy individuals and longitudinal samples from patients with Stage IV PDAC undergone treatment. The longitudinal samples were from 26 patients of which 16 were CA19-9 secretors (defined as &amp;gt;35 U/ml) and 10 were CA19-9 non-secretors (defined as &amp;lt;35 U/ml) that were treated with various regimens for 4-24 months with monthly blood sample collection and CT scans (a total of 305 samples). We found that the concentrations of ALPPL2+ and THBS2+ EVs are on average 1,737 and 1,113 times higher in PDAC patients than in the healthy controls, respectively. Correlation analysis using the mixed linear model showed that the concentrations of both ALPPL2+ and THBS2+ EVs significantly correlate with changes in tumor size (based on RECIST measurements) in the longitudinal samples of CA19-9 non-secretors or secretors. In CA19-9 non-secretors the correlation p values are 0.003 and 0.006 for ALPPL2+ and THBS2+ EVs, respectively, whereas in CA19-9 secretors, the p values are 0.014 and 0.016 for ALPPL2+ and THBS2+ EVs, respectively. Our data indicates that EV based ALPPL2 and THBS2 could potentially serve as biomarkers for disease monitoring in patients with PDAC. (This work was supported in part by the Dorrance Family Fund and the Flinn Foundation) Citation Format: Kuntal Halder, Gayle Jameson, Erkut Borazanci, Wei Lin, Dereck Cridebring, Daniel Von Hoff, Haiyong Han. Extracellular vesicle based ALPPL2 and THBS2 as biomarkers for disease monitoring in patients with pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2497.