Circulating exosomal noncoding RNAs as prognostic biomarkers in human hepatocellular carcinoma |
| |
| Authors: | Yu Rim Lee Gyeonghwa Kim Won Young Tak Se Young Jang Young Oh Kweon Jung Gil Park Hye Won Lee Young Seok Han Jae Min Chun Soo Young Park Keun Hur |
| |
| Affiliation: | 1. Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea;2. Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, South Korea;3. Department of Pathology, Keimyung University School of Medicine, Daegu, South Korea;4. Department of Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea;5. Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, South Korea |
| |
| Abstract: | 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. |
| |
| Keywords: | circulating biomarker exosome microRNA lncRNA hepatocellular carcinoma |
|
|
