Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response
by
Saori Itami-Matsumoto 1, Michiyo Hayakawa 1,†, Sawako Uchida-Kobayashi 1, Masaru Enomoto 1, Akihiro Tamori 1, Kazuyuki Mizuno 2, Hidenori Toyoda 2, Takeyuki Tamura 3, Tatsuya Akutsu 3
, Takahiro Ochiya 4, Norifumi Kawada 1 and Yoshiki Murakami 1,*,‡
Saori Itami-Matsumoto 1, Michiyo Hayakawa 1,†, Sawako Uchida-Kobayashi 1, Masaru Enomoto 1, Akihiro Tamori 1, Kazuyuki Mizuno 2, Hidenori Toyoda 2, Takeyuki Tamura 3, Tatsuya Akutsu 3, Takahiro Ochiya 4, Norifumi Kawada 1 and Yoshiki Murakami 1,*,‡
1
Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
2
Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki, Gifu 503-8502, Japan
3
Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan
4
Institute of Medical Science, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
*
Author to whom correspondence should be addressed.
†
Present affiliation: Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine 465, Kajiicho, Kawaramachi-hiroko-ji, Kamigyo-ku, Kyoto 602-8566, Japan.
‡
Present affiliation: Department of Molecular Pathology, Tokyo Medical University. 6-1-1, Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Biomedicines 2019, 7(4), 87; https://doi.org/10.3390/biomedicines7040087
Received: 18 September 2019 / Revised: 30 October 2019 / Accepted: 31 October 2019 / Published: 3 November 2019
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Pathogenesis and Therapeutic Strategies)
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.
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MDPI and ACS Style
Itami-Matsumoto, S.; Hayakawa, M.; Uchida-Kobayashi, S.; Enomoto, M.; Tamori, A.; Mizuno, K.; Toyoda, H.; Tamura, T.; Akutsu, T.; Ochiya, T.; Kawada, N.; Murakami, Y. Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response. Biomedicines 2019, 7, 87.
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