Woo Hyun Goo, Choi Ji-Hye, Yoon Sarah, Jee Byul A, Cho Eun Ju, Lee Jeong-Hoon, Yu Su Jong, Yoon Jung-Hwan, Yi Nam-Joon, Lee Kwang-Woong, Suh Kyung-Suk, Kim Yoon Jun
Department of Physiology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea.
Department of Biomedical Sciences, Graduate School, Ajou University, 164 Worldcup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea.
Nat Commun. 2017 Oct 10;8(1):839. doi: 10.1038/s41467-017-00991-w.
Hepatocellular carcinoma harbors numerous genomic and epigenomic aberrations of DNA copy numbers and DNA methylation. Transcriptomic deregulation by these aberrations plays key driver roles in heterogeneous progression of cancers. Here, we profile DNA copy numbers, DNA methylation, and messenger RNA expression levels from 64 cases of hepatocellular carcinoma specimens. We find that the frequencies of the aberrancies of the DNA copy-number-correlated (CNVcor) expression genes and the methylation-correlated expression (METcor) genes are co-regulated significantly. Multi-omics integration of the CNVcor and METcor genes reveal three prognostic subtypes of hepatocellular carcinoma, which can be validated by an independent data. The most aggressive subtype expressing stemness genes has frequent BAP1 mutations, implying its pivotal role in the aggressive tumor progression. In conclusion, our integrative analysis of genomic and epigenomic regulation provides new insights on the multi-layered pathobiology of hepatocellular carcinoma, which might be helpful in developing precision management for hepatocellular carcinoma patients.Hepatocellular carcinoma is known to harbour numerous genomic and epigenomic aberrations, driving transcriptomic deregulation. Here, the authors integrate genomic, epigenomic, and expression data to reveal three prognostic subtypes, providing insight to the pathobiology of hepatocellular carcinoma.
肝细胞癌存在大量DNA拷贝数和DNA甲基化方面的基因组及表观基因组畸变。这些畸变导致的转录组失调在癌症的异质性进展中发挥关键驱动作用。在此，我们分析了64例肝细胞癌标本的DNA拷贝数、DNA甲基化及信使核糖核酸表达水平。我们发现，DNA拷贝数相关（CNVcor）表达基因和甲基化相关表达（METcor）基因的畸变频率存在显著的共同调控。对CNVcor和METcor基因进行多组学整合，揭示了肝细胞癌的三种预后亚型，这可通过独立数据得到验证。表达干性基因的最具侵袭性亚型存在频繁的BAP1突变，这表明其在侵袭性肿瘤进展中起关键作用。总之，我们对基因组和表观基因组调控的综合分析为肝细胞癌的多层病理生物学提供了新见解，这可能有助于为肝细胞癌患者制定精准治疗方案。已知肝细胞癌存在大量基因组和表观基因组畸变，导致转录组失调。在此，作者整合基因组、表观基因组和表达数据，以揭示三种预后亚型，为肝细胞癌的病理生物学提供见解。
