Circulating exosomal noncoding RNAs as prognostic biomarkers in human hepatocellular carcinoma

被引：262

作者：

Lee, Yu Rim ^{[1
]}

Kim, Gyeonghwa ^{[2
]}

Tak, Won Young ^{[1
]}

Jang, Se Young ^{[1
]}

Kweon, Young Oh ^{[1
]}

Park, Jung Gil ^{[3
]}

Lee, Hye Won ^{[4
]}

Han, Young Seok ^{[5
]}

Chun, Jae Min ^{[5
]}

Park, Soo Young ^{[1
]}

Hur, Keun ^{[2
]}

机构：

[1] Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Dept Internal Med, Sch Med, 130 Dongdeok Ro, Daegu 41944, South Korea

[2] Kyungpook Natl Univ, Dept Biochem & Cell Biol, Cell & Matrix Res Inst, Sch Med, Daegu, South Korea

[3] Yeungnam Univ, Dept Internal Med, Coll Med, Daegu, South Korea

[4] Keimyung Univ, Sch Med, Dept Pathol, Daegu, South Korea

[5] Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Sch Med, Dept Surg, Daegu, South Korea

来源：

INTERNATIONAL JOURNAL OF CANCER | 2019年 / 144卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

circulating biomarker; exosome; microRNA; lncRNA; hepatocellular carcinoma; EXTRACELLULAR VESICLES; TUMOR-SUPPRESSOR; MICRORNAS; CANCER; SERUM; EXPRESSION; BIOGENESIS; MANAGEMENT; MECHANISM; DIAGNOSIS;

D O I：

10.1002/ijc.31931

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：1444 / 1452

页数：9

共 51 条

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