miRNA Profiling of Magnetic Nanopore–Isolated Extracellular Vesicles for the Diagnosis of Pancreatic Cancer

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 = 27 mice and a user-blinded validation set of = 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. 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. .

Evaluation of circulating small extracellular vesicles derived miRNAs as biomarkers of early colon cancer: a comparison with plasma total miRNAs

“…There is growing evidence suggested the potential role for sEVs in early detection of many diseases [27–30]. However, systematic screening of plasma sEVs derived early CC biomarkers has not yet been reported.…”

Circulating miRNA-1290 as a potential biomarker for response to chemoradiotherapy and prognosis of patients with advanced oral squamous cell carcinoma: A single-center retrospective study

“…7 Although considerable previous research on determining the usefulness of miRNA as biomarkers has focused on analysis of tissue specimens, other researchers have focused on circulating miRNA as a potential diagnostic and prognostic biomarker. [8][9][10] Recently, miR-1246 and miR-1290 were identified as tumor-initiating, cell-specific miRNAs in non-small cell lung cancer. 11,12 Moreover, serum miR-1246 and miR-1290 levels were correlated with the clinical response of patients with lung cancer who were receiving chemotherapies.…”

The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer

“…We previously reported that miR-30e could be transferred by cholangiocarcinoma (CCA) cell-derived EVs, and suppress recipient CCA cell invasion and migration (18). In PDAC, some investigators reported that EVencapsulated miRNAs, such as miR-196a, miR-1246, or miR-4644, could contribute to tumor development and play crucial roles in the diagnosis as tools of liquid biopsy (19)(20)(21). Therefore, we focused on identifying the mechanisms of ncRNA transfer by PDAC-derived EVs and investigated their contributions to PDAC development.…”