Research Paper Volume 12, Issue 17 pp 17062—17078
Evidence that dysplasia related microRNAs in Barrett’s esophagus target PD-L1 expression and contribute to the development of esophageal adenocarcinoma
- 1 Department of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- 2 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- 3 Oncology Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- 4 Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Received: May 21, 2020 Accepted: June 22, 2020 Published: September 9, 2020https://doi.org/10.18632/aging.103634
How to Cite
Copyright: © 2020 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Esophageal adenocarcinoma (EAC) is the cancer arising from the esophagus, which frequently develop from Barrett’s esophagus (BE). Extracellular vesicles (EVs), particularly exosomes, are nanosized vesicles of endosomal origin released from various types of cells that have been implicated in cancers. However, the significance of circulating exosomes during the progression of BE to EAC remains unknown. Sera exosmal microRNAs were profiled from 13 EAC and 12BE patients compared to 12 healthy controls. We found a substantial dysregulation of exosomal miRNA levels in BE compared to healthy control, and identified a unique signature of 24 up regulated and 14 down regulated miRNAs. Further validation showed exosomal miR-196a, -26b, -21, and -143 expression was significantly higher in BE and continued to have higher levels in EAC compared to healthy controls; while sera exosomal miR-378, -210, -205, and -200c-3p were significantly lower expressed in BE patients compared to compared to controls. Further, miR-378, -210, -205, and -200c-3p continue to have even lower levels in EAC patients compared to BE. Interestingly, sera expression levels of exosomal miR-15a, -16, and -193a-3p were significantly down regulated in BE PD-L1(+) patients; Sera exosomal miR-15a, -15b, -16, and -193a-3p expression levels in EAC PD-L1(+) patients were significantly lower (all p < 0.01) when compared to EAC PD-L1(-) patients. More importantly, the BE-EAC group had longitudinally decreased exosomal expression levels of miR-15a, -15b, -16, and -193a-3p from BE status to their EAC progression. In conclusion, distinct microRNA expression patterns were demonstrated in circulating exosomes from Barrett’s esophagus and esophageal adenocarcinoma; Furthermore exosomal microRNAs potentially targeting PD-L1 mRNA were down regulated in PD-L1 (+) BE and EAC patients.