Evaluation of Plasma Extracellular Vesicle MicroRNA Signatures for Lung Adenocarcinoma and Granuloma With Monte-Carlo Feature Selection Method

Extracellular Vesicle (EV) is a compilation of secreted vesicles, including micro vesicles, large oncosomes, and exosomes. It can be used in non-invasive diagnosis. MicroRNAs (miRNAs) processed by exosomes can be detected by liquid biopsy. To objectively evaluate the discriminative ability of miRNAs from whole plasma, EV and EV-free plasma, we analyzed the miRNA expression profiles in whole plasma, EV and EV-free plasma of 10 lung adenocarcinoma and 9 granuloma patients. With Monte-Carlo feature selection method, the top discriminative miRNAs in whole plasma, EV and EV-free plasma were identified, and they were quite different. Using the Repeated Incremental Pruning to Produce Error Reduction (RIPPER) method, we learned the classification rules: in whole plasma, granuloma patients did not express hsa-miR-223-3p while the lung adenocarcinoma patients expressed hsa-miR-223-3p; in EV, the hsa-miR-23b-3p was highly expressed in granuloma patients but not lung adenocarcinoma patients; in EV-free plasma, hsa-miR-376a-3p was expressed in granuloma patients but barely expressed in lung adenocarcinoma patients. For prediction performance, whole plasma had the highest weighted accuracy and EV outperformed EV-free plasma. Our results suggested that EV can be used as lung cancer biomarker. However, since it is less stable and not easy to detect, there are still technological difficulties to overcome.