Circulating exosomal noncoding RNAs as prognostic biomarkers in human hepatocellular carcinoma

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 elucid...

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Bibliographic Details
Published in:International journal of cancer 2019-03, Vol.144 (6), p.1444-1452
Main Authors: Lee, Yu Rim, Kim, Gyeonghwa, Tak, Won Young, Jang, Se Young, Kweon, Young Oh, Park, Jung Gil, Lee, Hye Won, Han, Young Seok, Chun, Jae Min, Park, Soo Young, Hur, Keun
Format: Article
Language:English
Subjects:
Aged
Biomarkers, Tumor - blood
Biomarkers, Tumor - metabolism
Cancer
Carcinoma, Hepatocellular - blood
Carcinoma, Hepatocellular - mortality
Carcinoma, Hepatocellular - pathology
Cell-Free Nucleic Acids - blood
Cell-Free Nucleic Acids - metabolism
circulating biomarker
Disease Progression
exosome
Exosomes
Exosomes - metabolism
Female
Follow-Up Studies
Hepatocellular carcinoma
Humans
Immunoblotting
Liver cancer
Liver Neoplasms - blood
Liver Neoplasms - mortality
Liver Neoplasms - pathology
lncRNA
Male
Medical prognosis
Medical research
Metastases
microRNA
MicroRNAs - blood
MicroRNAs - metabolism
Middle Aged
miRNA
Multivariate analysis
Nanoparticles
Neoplasm Invasiveness - pathology
Neoplasm Staging
Portal vein
Portal Vein - pathology
Prognosis
Progression-Free Survival
Prospective Studies
Rank tests
RNA, Long Noncoding - blood
RNA, Long Noncoding - metabolism
Survival
Therapeutic applications
Thromboembolism
Thrombosis
Venous Thrombosis - diagnosis
Venous Thrombosis - etiology
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Description
Summary: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. What's new? A growing body of evidence indicates that noncoding RNAs (ncRNAs), such as miRNAs and lncRNAs, play an important role in tumor progression and metastasis. Could particular ncRNAs also serve as serum biomarkers for cancer prognosis? In our study, the authors found that two specific ncRNAs in circulating exosomes were independent predictors of overall survival and disease progression in human hepatocellular carcinoma (HCC). These molecules might therefore provide valuable biomarkers to improve the clinical management of HCC, as well as potential therapeutic targets.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.31931