Pu Chunwen, Huang Hui, Wang Zhidong, Zou Wei, Lv Yuecai, Zhou Zhiyuan, Zhang Qiqi, Qiao Liang, Wu Fei, Shao Shujuan
Department of Biobank, The Affiliated Sixth People's Hospital of Dalian Medical University, Dalian, China.
The Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Front Physiol. 2018 Jul 17;9:930. doi: 10.3389/fphys.2018.00930. eCollection 2018.
The aim of this study was to observe the possible change of microRNAs (miRNAs) in serum extracellular vesicles (EVs) from hepatocellular carcinoma (HCC) patients. The serum EVs were purified from 17 healthy donors, 16 chronic hepatitis B (CHB) patients and 24 HCC patients. The sequenced microRNAs in the purified EVs were analyzed to obtain highly differentially expressed genes (DEGs). Finally, the expression pattern of DEGs was validated using qRT-PCR. We found that the expression of hsa-miR-21-5p and hsa-miR-144-3p were significantly higher in EVs and liver cancer tissues compared with serum and the distal liver tissues in HCC patients. The ratio of hsa-miR-144-3p/hsa-miR-21-5p was significantly decreased in the patients with CHB but significantly increased in patients with HCC developed from CHB ( < 0.05). Hsa-144-3p/hsa-miR-21-5p exhibited greater performance than alpha-fetoprotein (AUC 0.780, 95% CI 0.601-0.960, versus AUC 0.626, 95% CI 0.410-0.843) in ROC curve analysis. Extracellular vesicle-associated hsa-miR-21-5p and hsa-miR-144-3p are markedly elevated in serum of patients with HCC. The potential role of these microRNAs in the pathogenesis of HCC is worth of further study.
本研究旨在观察肝细胞癌（HCC）患者血清细胞外囊泡（EVs）中微小RNA（miRNAs）的可能变化。从17名健康供体、16名慢性乙型肝炎（CHB）患者和24名HCC患者中纯化血清EVs。对纯化后的EVs中测序的微小RNA进行分析，以获得高度差异表达基因（DEGs）。最后，使用qRT-PCR验证DEGs的表达模式。我们发现，与HCC患者的血清和肝远端组织相比，hsa-miR-21-5p和hsa-miR-144-3p在EVs和肝癌组织中的表达显著更高。CHB患者中hsa-miR-144-3p/hsa-miR-21-5p的比值显著降低，但CHB发展而来的HCC患者中该比值显著升高（<0.05）。在ROC曲线分析中，hsa-144-3p/hsa-miR-21-5p表现出比甲胎蛋白更好的性能（AUC 0.780，95%CI 0.601-0.960，对比AUC 0.626，95%CI 0.410-0.843）。细胞外囊泡相关的hsa-miR-21-5p和hsa-miR-144-3p在HCC患者血清中明显升高。这些微小RNA在HCC发病机制中的潜在作用值得进一步研究。
