Exosome-derived differentiation antagonizing non-protein coding RNA with risk of hepatitis C virus-related hepatocellular carcinoma recurrence

Shu-Chi Wang; Chia-Yang Li; Wen-Tsan Chang; Wei-Chung Cheng; Chia-Hung Yen; Wen-Yu Tu; Zu-Yau Lin; Ching-Chih Lin; Ming-Lun Yeh; Chung-Feng Huang; Jee-Fu Huang; Chia-Yen Dai; Wan-Long Chuang; Yao-Li Chen; Ming-Lung Yu

doi:10.1111/liv.14772

Exosome-derived differentiation antagonizing non-protein coding RNA with risk of hepatitis C virus-related hepatocellular carcinoma recurrence

Liver Int. 2021 May;41(5):956-968. doi: 10.1111/liv.14772. Epub 2021 Jan 23.

Authors

Shu-Chi Wang¹, Chia-Yang Li², Wen-Tsan Chang^{3

4}, Wei-Chung Cheng⁵, Chia-Hung Yen⁶, Wen-Yu Tu⁷, Zu-Yau Lin⁷, Ching-Chih Lin⁷, Ming-Lun Yeh^{7

8}, Chung-Feng Huang^{7

8}, Jee-Fu Huang^{7

8}, Chia-Yen Dai^{7

8}, Wan-Long Chuang^{7

8}, Yao-Li Chen^{3

9}, Ming-Lung Yu^{7

8}

Affiliations

¹ Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
² Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴ Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁵ Graduate Institute of Biomedical Science, Research Center for Cancer Biology, China Medical University, Taichung, Taiwan.
⁶ Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁷ Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁸ Faculty of Internal Medicine, School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁹ Transplant Medicine and Surgery Research Center, Changhua Christian Hospital, Changhua, Taiwan.

PMID: 33346937
DOI: 10.1111/liv.14772

Abstract

Background & aims: Differentiation antagonizing non-protein coding RNA is associated with various types of neoplasms. Hepatitis C virus-related hepatocellular carcinoma has a high risk of recurrence. Here we determined the role of differentiation antagonizing non-protein coding RNA in hepatitis C virus-related hepatocarcinogenesis and identified potential therapeutic targets and non-invasive prognostic markers for long-term outcome of hepatitis C virus-related hepatocellular carcinoma after surgical resection.

Methods: Differentiation antagonizing non-protein coding RNAs relevant to hepatitis C virus-related hepatocellular carcinoma were identified through comparative RNA-sequencing of tumour and adjacent non-tumour (ANT) tissues in a screening set, and were validated using real-time polymerase chain reaction. Target long non-coding RNAs (lncRNAs) in tissues and serum exosomes were used to predict the recurrence of hepatitis C virus-related hepatocellular carcinoma after curative surgical resection in a large application cohort from 2005 to 2012.

Results: We confirmed that differentiation antagonizing non-protein coding RNA was upregulated following hepatitis C virus infection and identified as the lncRNA most relevant to hepatitis C virus-related hepatocellular carcinoma in tumour tissues as compared to that in ANT tissues. In 183 hepatitis C virus-related hepatocellular carcinoma patients followed for 10 years after curative HCC resection, the expression level of circulating exosomal differentiation antagonizing non-protein coding RNA was positively associated with HCC recurrence and was the most predictive factor associated with HCC recurrence and mortality (hazard ratio/95% confidence intervals: 7.0/4.3-11.6 and 2.7/1.5-5.1 respectively).

Conclusions: Differentiation antagonizing non-protein coding RNA is highly relevant to disease progression of hepatitis C virus-related hepatocellular carcinoma. Our finding indicated that circulating exosomal differentiation antagonizing non-protein coding RNA might serve as a non-invasive prognostic biomarker for hepatitis C virus-related hepatocellular carcinoma.

Keywords: HCC; differentiation antagonizing non-protein coding RNA; exosomes; hepatitis C virus; recurrence.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular* / genetics
Exosomes* / genetics
Gene Expression Regulation, Neoplastic
Hepacivirus / genetics
Humans
Liver Neoplasms* / genetics
Neoplasm Recurrence, Local
RNA, Long Noncoding* / genetics

Substances

RNA, Long Noncoding