Genomic analysis of liver cancer unveils novel driver genes and distinct prognostic features
Publication in refereed journal

替代計量分析
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其它資訊
摘要Objective: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with a dismal prognosis. However, driver genes and prognostic markers in HCC remain to be identified. It is hoped that in-depth analysis of HCC genomes in relation to available clinicopathological information will give rise to novel molecular prognostic markers.

Methods: We collected genomic data of 1,061 HCC patients from previous studies, and performed integrative analysis to identify significantly mutated genes and molecular prognosticators. We employed three MutSig algorithms (MutSigCV, MutSigCL and MutSigFN) to identify significantly mutated genes. The GISTIC2 algorithm was used to delineate focally amplified and deleted genomic regions. Nonnegative matrix factorization (NMF) was utilized to decipher mutational signatures. Kaplan-Meier survival and Cox regression analyses were used to associate gene mutation and copy number alteration with survival outcome. Logistic regression model was applied to test association between gene mutation and mutational signatures.

Results: We discovered 11 novel driver genes, including RNF213, VAV3 and TNRC6B, with mutational prevalence ranging from 1% to 3%. Seven mutational signatures were also identified in HCC, some of which were associated with mutations of classical driver genes (e.g., TP53, TERT) as well as alcohol consumption. Focal amplifications of TERT and other druggable targets, including AURKA, were also revealed. Targeting AURKA by a small-molecule inhibitor potently induced apoptosis in HCC cells. We further demonstrated that HCC patients with TERT amplification displayed shortened overall survival independent of other clinicopathological parameters. In conclusion, our study identified novel cancer driver genes and prognostic markers in HCC, reiterating the translational importance of omics data in the precision medicine era.
出版社接受日期12.12.2017
著者Xiangchun Li, Weiqi Xu, Wei Kang, Sunny H. Wong, Mengyao Wang, Yong Zhou, Xiaodong Fang, Xiuqing Zhang, Huanming Yang, Chi H. Wong, Ka F. To, Stephen L. Chan, Matthew T.V. Chan, Joseph J.Y. Sung, William K.K. Wu, Jun Yu
期刊名稱Theranostics
出版年份2018
卷號8
期次6
頁次1740 - 1751
國際標準期刊號1838-7640
語言美式英語

上次更新時間 2020-15-08 於 02:34