Plasma Extracellular Vesicle-derived MicroRNA Associated with Human Alpha-1 Antitrypsin Deficiency-mediated Liver Disease

作者：Regina Oshins, Zhiguang Huo, Zachary Greenberg, Virginia Clark, Sergio Duarte, Huiping Zhou, Jesse West, Mei He, Mark Brantly, Nazli Khodayari · 发表于：Journal of Clinical and Translational Hepatology · 年份：2024 · DOI：10.14218/jcth.2024.00253 · 被引用次数：1 · 研究领域：Protease and Inhibitor Mechanisms、Extracellular vesicles in disease、GDF15 and Related Biomarkers

Background and Aims: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until its final stages when liver transplantation is the only available therapy. Biomarkers offer an advantage for disease evaluation. The presence of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) presents a noninvasive approach to assess the molecular signatures of the disease. In this study, we aimed to identify miRNA biomarkers to distinguish molecular signatures of the liver disease associated with AATD in AATD individuals. Methods: Using small RNA sequencing and qPCR, we examined plasma EV miRNAs in healthy controls (n = 20) and AATD patients (n = 17). We compared the EV miRNAs of AATD individuals with and without liver disease, developing an approach for detecting liver disease. A set of miRNAs identified in the AATD testing cohort was validated in a separate cohort of AATD patients (n = 45). Results: We identified differential expression of 178 EV miRNAs in the plasma of the AATD testing cohort compared to controls. We categorized AATD individuals into those with and without liver disease, identifying 39 differentially expressed miRNAs. Six miRNAs were selected to test their ability to discriminate liver disease in AATD. These were validated for their specificity and sensitivity in an independent cohort of 45 AATD individuals. Our logistic model established composi...