Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response
Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection patients (CH) results in a sustained viral response (SVR) in over 95% of patients. However, hepatocellular carcinoma (HCC) occurs in 1−5% of patients who achieved an SVR after treatment with interferon. We...
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doaj-6117457f9b024663bc80659eccf61e242020-11-25T00:05:32ZengMDPI AGBiomedicines2227-90592019-11-01748710.3390/biomedicines7040087biomedicines7040087Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral ResponseSaori Itami-Matsumoto0Michiyo Hayakawa1Sawako Uchida-Kobayashi2Masaru Enomoto3Akihiro Tamori4Kazuyuki Mizuno5Hidenori Toyoda6Takeyuki Tamura7Tatsuya Akutsu8Takahiro Ochiya9Norifumi Kawada10Yoshiki Murakami11Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, JapanDepartment of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, JapanDepartment of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, JapanDepartment of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, JapanDepartment of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, JapanDepartment of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki, Gifu 503-8502, JapanDepartment of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki, Gifu 503-8502, JapanBioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, JapanBioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, JapanInstitute of Medical Science, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, JapanDepartment of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, JapanDepartment of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, JapanDirect-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection patients (CH) results in a sustained viral response (SVR) in over 95% of patients. However, hepatocellular carcinoma (HCC) occurs in 1−5% of patients who achieved an SVR after treatment with interferon. We attempted to develop a minimally invasive and highly reliable method of predicting the occurrence and recurrence of HCC in patients who achieved an SVR with DAA therapy. The exosomal miRNA expression patterns of 69 CH patients who underwent HCC curative treatment and 70 CH patients were assessed using microarray analysis. We identified a miRNA expression pattern characteristic of SVR-HCC by using machine learning. Twenty-five of 69 patients had HCC recurrence. The expression of four exosomal miRNAs predicted HCC recurrence with 85.3% accuracy. Fifteen of 70 patients had HCC occurrence. The expression of four exosomal miRNAs predicted the onset of HCC with 85.5% accuracy. The expression patterns of miR-4718, 642a-5p, 6826-3p, and 762 in exosomes were positively correlated with those in the liver, and downregulation of these miRNAs induced cell proliferation and prevented apoptosis in vitro. Aberrant expression of four miRNAs, which was used for prediction, was associated with HCC onset after HCV eradication. Expression patterns of exosomal miRNAs are a promising tool to predict SVR-HCC.https://www.mdpi.com/2227-9059/7/4/87sustained viral responsedirect-acting antiviral therapymirnaexosomemicroarray |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Saori Itami-Matsumoto Michiyo Hayakawa Sawako Uchida-Kobayashi Masaru Enomoto Akihiro Tamori Kazuyuki Mizuno Hidenori Toyoda Takeyuki Tamura Tatsuya Akutsu Takahiro Ochiya Norifumi Kawada Yoshiki Murakami |
spellingShingle |
Saori Itami-Matsumoto Michiyo Hayakawa Sawako Uchida-Kobayashi Masaru Enomoto Akihiro Tamori Kazuyuki Mizuno Hidenori Toyoda Takeyuki Tamura Tatsuya Akutsu Takahiro Ochiya Norifumi Kawada Yoshiki Murakami Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response Biomedicines sustained viral response direct-acting antiviral therapy mirna exosome microarray |
author_facet |
Saori Itami-Matsumoto Michiyo Hayakawa Sawako Uchida-Kobayashi Masaru Enomoto Akihiro Tamori Kazuyuki Mizuno Hidenori Toyoda Takeyuki Tamura Tatsuya Akutsu Takahiro Ochiya Norifumi Kawada Yoshiki Murakami |
author_sort |
Saori Itami-Matsumoto |
title |
Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response |
title_short |
Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response |
title_full |
Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response |
title_fullStr |
Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response |
title_full_unstemmed |
Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response |
title_sort |
circulating exosomal mirna profiles predict the occurrence and recurrence of hepatocellular carcinoma in patients with direct-acting antiviral-induced sustained viral response |
publisher |
MDPI AG |
series |
Biomedicines |
issn |
2227-9059 |
publishDate |
2019-11-01 |
description |
Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection patients (CH) results in a sustained viral response (SVR) in over 95% of patients. However, hepatocellular carcinoma (HCC) occurs in 1−5% of patients who achieved an SVR after treatment with interferon. We attempted to develop a minimally invasive and highly reliable method of predicting the occurrence and recurrence of HCC in patients who achieved an SVR with DAA therapy. The exosomal miRNA expression patterns of 69 CH patients who underwent HCC curative treatment and 70 CH patients were assessed using microarray analysis. We identified a miRNA expression pattern characteristic of SVR-HCC by using machine learning. Twenty-five of 69 patients had HCC recurrence. The expression of four exosomal miRNAs predicted HCC recurrence with 85.3% accuracy. Fifteen of 70 patients had HCC occurrence. The expression of four exosomal miRNAs predicted the onset of HCC with 85.5% accuracy. The expression patterns of miR-4718, 642a-5p, 6826-3p, and 762 in exosomes were positively correlated with those in the liver, and downregulation of these miRNAs induced cell proliferation and prevented apoptosis in vitro. Aberrant expression of four miRNAs, which was used for prediction, was associated with HCC onset after HCV eradication. Expression patterns of exosomal miRNAs are a promising tool to predict SVR-HCC. |
topic |
sustained viral response direct-acting antiviral therapy mirna exosome microarray |
url |
https://www.mdpi.com/2227-9059/7/4/87 |
work_keys_str_mv |
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