American Association for Cancer Research
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Figure S2 from miRNA Profiling of Magnetic Nanopore–Isolated Extracellular Vesicles for the Diagnosis of Pancreatic Cancer

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journal contribution
posted on 2023-03-31, 02:00 authored by Jina Ko, Neha Bhagwat, Taylor Black, Stephanie S. Yee, Young-Ji Na, Stephen Fisher, Junhyong Kim, Erica L. Carpenter, Ben Z. Stanger, David Issadore

Significantly enriched pathways from the 11 identified miRNA markers.

Funding

Pennsylvania Department of Health Commonwealth Universal Research Enhancement Program

NIH

Pancreatic Cancer Action Network Translational Research Award

Abramson Cancer Center Pancreatic Translational Center of Excellence

Penn Center for Molecular Studies in Digestive and Liver Diseases

National Institute of Diabetes and Digestive and Kidney Diseases

American Cancer Society

USAMRMC

History

ARTICLE ABSTRACT

Improved diagnostics for pancreatic ductal adenocarcinoma (PDAC) to detect the disease at earlier, curative stages and to guide treatments is crucial to progress against this disease. The development of a liquid biopsy for PDAC has proven challenging due to the sparsity and variable phenotypic expression of circulating biomarkers. Here we report methods we developed for isolating specific subsets of extracellular vesicles (EV) from plasma using a novel magnetic nanopore capture technique. In addition, we present a workflow for identifying EV miRNA biomarkers using RNA sequencing and machine-learning algorithms, which we used in combination to classify distinct cancer states. Applying this approach to a mouse model of PDAC, we identified a biomarker panel of 11 EV miRNAs that could distinguish mice with PDAC from either healthy mice or those with precancerous lesions in a training set of n = 27 mice and a user-blinded validation set of n = 57 mice (88% accuracy in a three-way classification). These results provide strong proof-of-concept support for the feasibility of using EV miRNA profiling and machine learning for liquid biopsy.Significance: These findings present a panel of extracellular vesicle miRNA blood-based biomarkers that can detect pancreatic cancer at a precancerous stage in a transgenic mouse model. Cancer Res; 78(13); 3688–97. ©2018 AACR.