Plasma miRNAs as early biomarkers for detecting hepatocellular carcinoma

Yang Wen, Jing Han, Jianguo Chen, Jing Dong, Yongxiang Xia, Jibin Liu, Yue Jiang, Juncheng Dai, Jianhua Lu, Guangfu Jin, Jiali Han, Qingyi Wei, Hongbing Shen, Beicheng Sun, Zhibin Hu

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

The early detection of hepatocellular carcinoma (HCC) presents a challenge because of the lack of specific biomarkers. Serum/plasma microRNAs (miRNAs) can discriminate HCC patients from controls. We aimed to identify and evaluate HCC-associated plasma miRNAs originating from the liver as early biomarkers for detecting HCC. In this multicenter three-phase study, we first performed screening using both plasma (HCC before and after liver transplantation or liver hepatectomy) and tissue samples (HCC, para-carcinoma and cirrhotic tissues). Then, we evaluated the diagnostic potential of the miRNAs in two case-control studies (training and validation sets). Finally, we used two prospective cohorts to test the potential of the identified miRNAs for the early detection of HCC. During the screening phase, we identified ten miRNAs, eight of which (miR-20a-5p, miR-25-3p, miR-30a-5p, miR-92a-3p, miR-132-3p, miR-185-5p, miR-320a and miR-324-3p) were significantly overexpressed in the HBV-positive HCC patients compared with the HBV-positive cancer-free controls in both the training and validation sets, with a sensitivity of 0.866 and specificity of 0.646. Furthermore, we assessed the potential for early HCC detection of these eight newly identified miRNAs and three previously reported miRNAs (miR-192-5p, miR-21-5p and miR-375) in two prospective cohorts. Our meta-analysis revealed that four miRNAs (miR-20a-5p, miR-320a, miR-324-3p and miR-375) could be used as preclinical biomarkers (pmeta < 0.05) for HCC. The expression profile of the eight-miRNA panel can be used to discriminate HCC patients from cancer-free controls, and the four-miRNA panel (alone or combined with AFP) could be a blood-based early detection biomarker for HCC screening.

Original languageEnglish (US)
Pages (from-to)1679-1690
Number of pages12
JournalInternational Journal of Cancer
Volume137
Issue number7
DOIs
StatePublished - Jan 1 2015

Keywords

  • biomarker
  • early detection
  • hepatocellular carcinoma
  • miRNA
  • plasma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Wen, Y., Han, J., Chen, J., Dong, J., Xia, Y., Liu, J., Jiang, Y., Dai, J., Lu, J., Jin, G., Han, J., Wei, Q., Shen, H., Sun, B., & Hu, Z. (2015). Plasma miRNAs as early biomarkers for detecting hepatocellular carcinoma. International Journal of Cancer, 137(7), 1679-1690. https://doi.org/10.1002/ijc.29544