Exosomal miR-320c as a Potential Biomarker of Bronchopulmonary Dysplasia at Early Stage: A Pilot Study

Abstract

Background: Bronchopulmonary dysplasia has become one of the most common adverse outcomes in premature infants, however, the pathogenesis remains unanswered. This was a prospective pilot study to investigate potential biomarkers of the development of bronchopulmonary dysplasia, which could help in the understanding and management of this disease. Methods: Exosomes were separated from the sputum samples of bronchopulmonary dysplasia patients at 28 days of life (early group) and the time when bronchopulmonary dysplasia was diagnosed (confirmed group). Exosomal micro-RNA was compared with a control group to find differentially expressed micro-RNA. Results: Microvesicles isolated from sputum samples of three groups were assessed by transmission electron microscopy, particle size analysis, as well as flow cytometry. The shape and size of the isolated vesicles from the three groups all matched the typical appearance of exosomes. The micro vesicles isolated from the sputum samples expressed clusters of differentiation (CD), the exosomal biomarkers strikingly, including CD63, CD9, and CD8. There were 1308 exosomal micro-RNA captured in total, in which, miR-320c (micro-RNA 320c) was significantly upregulated in the patients with bronchopulmonary dysplasia, starting at 28 days of age. Compared with the control group, the p value was 0.0046 in the early group and 0.021 in the confirmed group, respectively. There was no significant difference in the expression of miR-320c between the early and confirmed bronchopulmonary dysplasia groups (p = 0.062). Conclusions: The up-regulation of exosomal micro-RNA 320c may serve as a potential biomarker in the early stage of bronchopulmonary dysplasia.