MicroRNA expression in hepatocellular carcinoma after the eradication of chronic hepatitis virus C infection using interferon therapy

Akihiro Tamori; Yoshiki Murakami; Shoji Kubo; Saori Itami; Sawako Uchida-Kobayashi; Hiroyasu Morikawa; Masaru Enomoto; Shigekazu Takemura; Toshihito Tanahashi; Y-H Taguchi; Norifumi Kawada

doi:10.1111/hepr.12518

MicroRNA expression in hepatocellular carcinoma after the eradication of chronic hepatitis virus C infection using interferon therapy

Hepatol Res. 2016 Mar;46(3):E26-35. doi: 10.1111/hepr.12518. Epub 2015 Apr 27.

Affiliations

¹ Department of Hepatology, Osaka City University Graduate School of Medicine.
² Department of Hepatobiliary Surgery, Osaka City University Graduate School of Medicine, Osaka.
³ Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe.
⁴ Department of Physics, Chuo University, Tokyo, Japan.

PMID: 25788219
DOI: 10.1111/hepr.12518

Abstract

Aim: Hepatocellular carcinoma (HCC) develops in up to 5% of patients after the successful treatment of chronic hepatitis C virus (HCV) infection using interferon therapy. The aim of this study was to characterize miRNA expression in liver tissues from patients who achieved a sustained viral response (SVR).

Methods: Seventy-one patients with resected HCC were enrolled into the present study: 61 HCC from patients with continuously infected HCV (HCV-HCC) and 10 from patients who had achieved SVR (SVR-HCC). We also included non-tumor tissues (SVR-NT) from four patients with SVR-HCC, and liver tissue (SVR-CH) from four SVR patients without HCC. Total RNA was extracted from liver samples. The miRNA expression patterns were analyzed using microarrays. In addition, target gene expression was quantified after miRNA overexpression in HEK293 cells.

Results: We could discriminate between SVR-HCC and HCV-HCC with 75.36% accuracy using the expression pattern of six specific miRNA. The expression levels of 37 miRNA were significantly lower in HCV-HCC than in SVR-HCC, whereas the expression of 25 miRNA was significantly higher in HCV-HCC than SVR-HCC (P < 1.0E-05). The expression of thrombospondin 1 was regulated in an opposing manner by miR-30a-3p in SVR-HCC and HCV-HCC. In non-tumor tissues, the expression pattern of seven miRNA could distinguish between SVR-CH and SVR-NT with 87.50% accuracy.

Conclusion: Comprehensive miRNA expression analyses could not only differentiate between SVR-HCC and HCV-HCC but also forecast hepatocarcinogenesis after achieving SVR.

Keywords: hepatitis C virus; hepatocellular carcinoma; interferon; miRNA; sustained viral response.