Abstract A039: Beta-sheet richness of extracellular vesicles for pancreatic cancer screening

Abstract

Abstract Pancreatic cancer patients predominantly present with advanced disease at the time of diagnosis, which is the reason for its high mortality. A noninvasive fast-screening method to detect asymptomatic early-stage disease is an unmet need. Tumor-derived extracellular vesicles (EVs) bearing information from parental cells were believed to be a good candidate for noninvasive diagnosis biomarkers. Many pancreatic cancer diagnostic assays use only a single cancer-associated marker/signature, which are either subtype-specific or could be easily masked by high background signals. The purpose of this research is to develop a fast method of noninvasive diagnosis biomarkers for pancreatic cancer screening as collective attribute by analyzing the secondary structure of the EV proteins using circular dichroism (CD), Fourier transform infrared (FT-IR), and fluorescent staining. We developed a high-throughput noninvasive assay by using the β-sheet richness (BR) of the tumor-derived EVs as a target in order to recognize EVs originating from malignant and nonmalignant cells. Extracellular vesicles bearing information from parental cells, play important roles in cell−cell signaling, immune response, and metastasis. We were able to indicate that pancreatic cancer EV proteins were more β-sheet-rich than their healthy counterparts. A fast method assay was developed that combines immunoprecipitation (IP) and Thioflavin T (ThT) fluorescent dye, termed as EvIPThT, that binds directly to β-sheet-rich proteins into EVs. This assay readout of a review pilot companion showed adequate biased power contrasting samples from cancer cases, disease controls and healthy controls. This method appeared to be the simple, inexpensive, low sample, less time consuming, high-throughput, and automatable, since no β-sheet richness change was observed in the treated and nontreated cells, EvIPThT assay shows promising results as a pancreatic cancer screening assay, filling the translational gaps left by current EV detection methods. Citation Format: Komila Rasuleva, Dali Sun. Beta-sheet richness of extracellular vesicles for pancreatic cancer screening [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A039.