Circulating exosomal noncoding RNAs as prognostic biomarkers in human hepatocellular carcinoma
Circulating exosomal noncoding RNAs as prognostic biomarkers in human hepatocellular carcinoma
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DOI：
10.1002/ijc.31931
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发表时间：
2019-03-15
影响因子：
6.4
通讯作者：
Hur, Keun
中科院分区：
文献类型：
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作者：
Lee, Yu Rim;Kim, Gyeonghwa;Hur, Keun
胞外体非编码RNA(NcRNAs)具有独特的表达谱，反映了肿瘤的特征，其在肿瘤进展和转移中的作用正在显现。然而，循环胞外体ncRNAs在肝细胞癌(HCC)预后中的意义仍有待阐明。因此，我们确定了循环外体ncRNAs(miRNA-21和lncRNA-ATB)对人肝细胞癌的预后意义。这项前瞻性研究纳入了2014年10月至2015年9月期间的79名肝癌患者。用ExoQuick Exosome沉淀液从血清样本中提取Exosome。为了验证从血清中分离外切体的有效性，进行了外切体标记的免疫印迹和纳米颗粒的NanoSight表征。用miRNasy血清/血浆微量试剂盒从外体中分离出ncRNAs。循环外体miRNA-21和lncRNA-ATB均与TNM分期和其他预后因素有关，包括T分期和门静脉血栓形成。用COX回归检验进行的多变量分析表明，高miRNA-21和高lncRNA-ATB都是死亡率和疾病进展的独立预测因子，以及较大的肿瘤大小和较高的C反应蛋白(均P<；0.05)。循环中外体miRNA-21和lncRNA-atb水平较高的患者总体生存率和无进展生存率显著降低(对数等级检验：P<；0.0016)。总之，我们的研究提供了强有力的证据，表明循环外体ncRNAs(miRNA-21和lncRNA-ATB)是新的肝癌预后标志物和治疗靶点。
Exosomal noncoding RNAs (ncRNAs) have unique expression profiles reflecting the characteristics of a tumor, and their role in tumor progression and metastasis is emerging. However, the significance of circulating exosomal ncRNAs in the prognosis of hepatocellular carcinoma (HCC) remains to be elucidated. We therefore determined the prognostic significance of circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) for human HCC. This prospective study enrolled 79 HCC patients between October 2014 and September 2015. Exosomes were extracted from serum samples using the ExoQuick Exosome Precipitation Solution. To validate the isolation of the exosomes from serum, immunoblotting for exosome markers and characterization of nanoparticle using NanoSight were performed. NcRNAs were isolated from exosomes using the miRNeasy serum/plasma micro kit. Both circulating exosomal miRNA-21 and lncRNA-ATB were related to TNM stage and other prognostic factors, including the T stage and portal vein thrombosis. Multivariate analysis using the Cox regression test identified that both higher miRNA-21 and higher lncRNA-ATB were independent predictors of mortality and disease progression, along with larger tumor size and higher C-reactive protein (all p < 0.05). The overall survival and progression-free survival were significantly lower in patients with higher circulating levels of exosomal miRNA-21 (>= 0.09) and lncRNA-ATB (>= 0.0016) (log-rank test: p < 0.05). In conclusion, our study has provided strong evidence that circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) are novel prognostic markers and therapeutic targets for HCC.