論文

2021年5月28日

Oncogenic transcriptomic profile is sustained in the liver after the eradication of the hepatitis C virus

Carcinogenesis
  • Haruhiko Takeda
  • Atsushi Takai
  • Eriko Iguchi
  • Masako Mishima
  • Soichi Arasawa
  • Ken Kumagai
  • Yuji Eso
  • Takahiro Shimizu
  • Ken Takahashi
  • Yoshihide Ueda
  • Kojiro Taura
  • Etsuro Hatano
  • Hiroko Iijima
  • Haruyo Aoyagi
  • Hideki Aizaki
  • Hiroyuki Marusawa
  • Takaji Wakita
  • Hiroshi Seno
  • 全て表示

42
5
開始ページ
672
終了ページ
684
記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/carcin/bgab014
出版者・発行元
Oxford University Press (OUP)

<title>Abstract</title>
Hepatocellular carcinoma (HCC) developing after hepatitis C virus (HCV) eradication is a serious clinical concern. However, molecular basis for the hepatocarcinogenesis after sustained virologic response (SVR) remains unclear. In this study, we aimed to unveil the transcriptomic profile of post-SVR liver tissues and explore the molecules associated with post-SVR carcinogenesis. We analysed 90 RNA sequencing datasets, consisting of non-cancerous liver tissues including 20 post-SVR, 40 HCV-positive and 7 normal livers, along with Huh7 cell line specimens before and after HCV infection and eradication. Comparative analysis demonstrated that cell cycle- and mitochondrial function-associated pathways were altered only in HCV-positive non-cancerous liver tissues, whereas some cancer-related pathways were up-regulated in the non-cancerous liver tissues of both post-SVR and HCV-positive cases. The persistent up-regulation of carcinogenesis-associated gene clusters after viral clearance was reconfirmed through in vitro experiments, of which, CYR61, associated with liver fibrosis and carcinogenesis in several cancer types, was the top enriched gene and co-expressed with cell proliferation-associated gene modules. To evaluate whether this molecule could be a predictor of hepatocarcinogenesis after cure of HCV infection, we also examined 127 sera from independent HCV-positive cohorts treated with direct-acting antivirals (DAAs), including 60 post-SVR-HCC patients, and found that the elevated serum Cyr61 was significantly associated with early carcinogenesis after receiving DAA therapy. In conclusion, some oncogenic transcriptomic profiles are sustained in liver tissues after HCV eradication, which might be a molecular basis for the liver cancer development even after viral clearance. Among them, up-regulated CYR61 could be a possible biomarker for post-SVR-HCC.

リンク情報
DOI
https://doi.org/10.1093/carcin/bgab014
URL
http://academic.oup.com/carcin/advance-article-pdf/doi/10.1093/carcin/bgab014/37254839/bgab014.pdf
URL
http://academic.oup.com/carcin/article-pdf/42/5/672/38374875/bgab014.pdf
ID情報
  • DOI : 10.1093/carcin/bgab014
  • ISSN : 0143-3334
  • eISSN : 1460-2180

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