These authors contributed equally to this work.
Clinical significance of the ubiquitin ligase UBE3C in hepatocellular carcinoma revealed by exome sequencing
Article first published online: 2 MAY 2014
© 2014 by the American Association for the Study of Liver Diseases
Volume 59, Issue 6, pages 2216–2227, June 2014
How to Cite
Jiang, J.-H., Liu, Y.-F., Ke, A.-W., Gu, F.-M., Yu, Y., Dai, Z., Gao, Q., Shi, G.-M., Liao, B.-Y., Xie, Y.-H., Fan, J., Huang, X.-W. and Zhou, J. (2014), Clinical significance of the ubiquitin ligase UBE3C in hepatocellular carcinoma revealed by exome sequencing. Hepatology, 59: 2216–2227. doi: 10.1002/hep.27012
Potential conflict of interest: Nothing to report.
Supported by the National Science Foundation for Distinguished Young Scholars of China (Grant No. 81225019), the National Natural Science Foundation of China (Grant No. 30872503, 81172277, 81071992, 81172023), and the National Key Sci-Tech Special Project of China (Grant No. 2012ZX10002-016).
- Issue published online: 28 MAY 2014
- Article first published online: 2 MAY 2014
- Accepted manuscript online: 15 JAN 2014 04:03AM EST
- Manuscript Accepted: 10 JAN 2014
- Manuscript Received: 5 JUN 2013
Virus-induced hepatocarcinogenesis involves a series of histological developmental processes with the stepwise acquisition of several genetic changes that are necessary for the malignant transformation of hepatocytes. Although genetic alterations are known to be involved in the pathogenesis of hepatocellular carcinoma (HCC), little is known about the contributions of specific genes to this process. To gain insight into the genetic alterations involved in the neoplastic evolution from chronic hepatitis B virus infection to dysplastic nodules (DN) to HCC, we captured and sequenced the exomes of four DNA samples: one DN sample, two HCC samples, and one control peripheral blood sample from a single HCC patient. Mutations in the UBE3C gene (encoding ubiquitin ligase E3C) were observed in both tumor tissues. Then we resequenced the UBE3C gene in a cohort of 105 HCC patients and identified mutations in 17 out of a total of 106 (16.0%) HCC patients. The subsequent experiments showed that UBE3C promoted HCC progression by regulating HCC cells epithelial-mesenchymal transition. Clinically, a tissue microarray study of a cohort containing 323 HCC patients revealed that the overexpression of UBE3C in primary HCC tissues correlated with decreased survival (hazard ratio [HR] = 1.657, 95% confidence interval [CI] = 1.220-2.251, P = 0.001) and early tumor recurrence (HR = 1.653, 95% CI = 1.227-2.228, P = 0.001) in postoperative HCC patients. Conclusion: Our findings indicate that UBE3C is a candidate oncogene involved in tumor development and progression and therefore a potential therapeutic target in applicable HCC patients. (Hepatology 2014;59:2216–2227)