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Int J Cancer. 2015 Oct 1;137(7):1679-90. doi: 10.1002/ijc.29544. Epub 2015 Apr 21.

Plasma miRNAs as early biomarkers for detecting hepatocellular carcinoma.

Wen Y1,2, Han J1,2, Chen J3,4, Dong J1, Xia Y5, Liu J4, Jiang Y1,2, Dai J1,2, Lu J3, Jin G1, Han J6, Wei Q7, Shen H1,2, Sun B5, Hu Z1,2.

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Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Department of Epidemiology, State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Department of Epidemiology, Qidong Liver Cancer Institute, Qidong, Jiangsu Province, China.
Department of Epidemiology, Nantong Tumor Hospital, Tumor Institute, Nantong, Jiangsu Province, China.
Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN.
Department of Epidemiology, Duke Cancer Institute, Duke University Medical Center, Durham, NC.


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.


biomarker; early detection; hepatocellular carcinoma; miRNA; plasma

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