慢性乙型肝炎病毒感染所致严重肝损伤中血清来源细胞外囊泡的表征及微小RNA表达分析
Characterization and microRNA Expression Analysis of Serum-Derived Extracellular Vesicles in Severe Liver Injury from Chronic HBV Infection.
作者信息
Liu Min, Liu Xionghao, Pan Mengmeng, Zhang Yu, Tang Xiangling, Liu Wanxi, Zhao Mingri, Ma Jing, Zhou Ning, Jiang Yongfang, Wang Wenlong, Liu Mujun
机构信息
Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, China.
Hunan Key Laboratory of Basic and Applied Hematology, Central South University, Changsha 410078, China.
出版信息
Life (Basel). 2023 Jan 28;13(2):347. doi: 10.3390/life13020347.
BACKGROUND
Extracellular vesicle (EV) microRNAs have been documented in several studies to have significantly different expressions in hepatitis B virus (HBV)-related liver diseases, such as hepatocellular carcinoma (HCC). The current work aimed to observe the characteristics of EVs and EV miRNA expressions in patients with severe liver injury chronic hepatitis B (CHB) and patients with HBV-associated decompensated cirrhosis (DeCi).
METHODS
The characterization of the EVs in the serum was carried out for three different groups, namely, patients with severe liver injury-CHB, patients with DeCi, and healthy controls. EV miRNAs were analyzed using miRNA-seq and RT-qPCR arrays. Additionally, we assessed the predictive and observational values of the miRNAs with significant differential expressions in serum EVs.
RESULTS
Patients with severe liver injury-CHB had the highest EV concentrations when compared to the normal controls (NCs) and patients with DeCi ( < 0.001). The miRNA-seq of the NC and severe liver injury-CHB groups identified 268 differentially expressed miRNAs (|FC| > 2, < 0.05). In this case, 15 miRNAs were verified using RT-qPCR, and it was found that novel-miR-172-5p and miR-1285-5p in the severe liver injury-CHB group showed marked downregulation in comparison to the NC group ( < 0.001). Furthermore, compared with the NC group, three EV miRNAs (novel-miR-172-5p, miR-1285-5p, and miR-335-5p) in the DeCi group showed various degrees of downregulated expression. However, when comparing the DeCi group with the severe liver injury-CHB group, only the expression of miR-335-5p in the DeCi group decreased significantly ( < 0.05). For the severe liver injury-CHB and DeCi groups, the addition of miR-335-5p improved the predictive accuracy of the serological levels, while miR-335-5p was significantly correlated with ALT, AST, AST/ALT, GGT, and AFP. The patients with severe liver injury-CHB had the highest number of EVs. The combination of novel-miR-172-5p and miR-1285-5p in serum EVs helped in predicting the progression of the NCs to severe liver injury-CHB, while the addition of EV miR-335-5p improved the serological accuracy of predicting the progression of severe liver injury-CHB to DeCi.
背景
多项研究已证明，细胞外囊泡（EV）中的微小RNA在乙型肝炎病毒（HBV）相关肝病（如肝细胞癌（HCC））中具有显著不同的表达。当前研究旨在观察重度肝损伤慢性乙型肝炎（CHB）患者和HBV相关失代偿期肝硬化（DeCi）患者的EV特征及EV微小RNA表达情况。
方法
对三个不同组别的血清EV进行特征分析，即重度肝损伤-CHB患者、DeCi患者和健康对照者。使用微小RNA测序（miRNA-seq）和逆转录定量聚合酶链反应（RT-qPCR）阵列分析EV微小RNA。此外，我们评估了血清EV中具有显著差异表达的微小RNA的预测和观察价值。
结果
与正常对照（NC）和DeCi患者相比，重度肝损伤-CHB患者的EV浓度最高（<0.001）。NC组和重度肝损伤-CHB组的miRNA-seq鉴定出268个差异表达的微小RNA（|FC|>2，<0.05）。在此情况下，使用RT-qPCR验证了15个微小RNA，发现重度肝损伤-CHB组中的新型-miR-172-5p和miR-1285-5p与NC组相比呈现明显下调（<0.001）。此外，与NC组相比，DeCi组中的三种EV微小RNA（新型-miR-172-5p、miR-1285-5p和miR-335-5p）呈现不同程度的下调表达。然而，将DeCi组与重度肝损伤-CHB组进行比较时，仅DeCi组中miR-335-5p的表达显著降低（<0.05）。对于重度肝损伤-CHB组和DeCi组，添加miR-335-5p可提高血清学水平的预测准确性，而miR-335-5p与丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、AST/ALT、γ-谷氨酰转移酶（GGT）和甲胎蛋白（AFP）显著相关。重度肝损伤-CHB患者的EV数量最多。血清EV中新型-miR-172-5p和miR-1285-5p的组合有助于预测NC进展为重度肝损伤-CHB，而添加EV miR-335-5p可提高预测重度肝损伤-CHB进展为DeCi的血清学准确性。
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