Hypoxia associated multi-omics molecular landscape of tumor tissue in patients with hepatocellular carcinoma.
Hypoxia associated multi-omics molecular landscape of tumor tissue in patients with hepatocellular carcinoma.
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肝细胞癌患者肿瘤组织缺氧相关的多组学分子景观
DOI：
10.18632/aging.202723
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发表时间：
2021-03-10
期刊：
影响因子：
--
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Zhang Q;Qiao L;Liu Q;Kong X;Hu J;Hu W;Wu Z;Li M;Liu L
本研究旨在更新有关肝细胞癌（HCC）组织中缺氧相关多组学分子景观的知识。收集了来自多个中心的大型 HCC 数据集。使用我们之前研究中构建的新型 HCC 特异性缺氧评分系统来评估 10 个 HCC 队列患者肿瘤组织的缺氧暴露。进行了全面的生物信息分析，以比较高缺氧评分和低缺氧评分患者的缺氧相关多组学分子特征。我们发现不同缺氧暴露水平的患者在转录组、基因组、表观基因组和蛋白质组改变方面存在显着差异，包括mRNA、微小RNA（miR）和长非编码RNA（lncRNA）表达的差异、拷贝数改变（CNA）的差异、DNA甲基化水平的差异、RNA选择性剪接事件的差异以及蛋白质水平的差异。鉴定了与 HCC 生存相关的分子事件。还探索了与缺氧相关的分子特征之间的潜在相关性，并构建了各种网络。我们揭示了肿瘤组织中特别全面的缺氧相关分子景观，为解释缺氧在肝癌中的作用提供了新的证据和观点。在临床上，本研究获得的数据可能有助于为不同缺氧水平的 HCC 患者制定个体化治疗或管理策略。
The present study was designed to update the knowledge about hypoxia-related multi-omic molecular landscape in hepatocellular carcinoma (HCC) tissues. Large-size HCC datasets from multiple centers were collected. The hypoxia exposure of tumor tissue from patients in 10 HCC cohorts was estimated using a novel HCC-specific hypoxia score system constructed in our previous study. A comprehensive bioinformatical analysis was conducted to compare hypoxia-associated multi-omic molecular features in patients with a high hypoxia score to a low hypoxia score. We found that patients with different exposure to hypoxia differed significantly in transcriptomic, genomic, epigenomic, and proteomic alterations, including differences in mRNA, microRNA (miR), and long non-coding RNA (lncRNA) expression, differences in copy number alterations (CNAs), differences in DNA methylation levels, differences in RNA alternative splicing events, and differences in protein levels. HCC survival- associated molecular events were identified. The potential correlation between molecular features related to hypoxia has also been explored, and various networks have been constructed. We revealed a particularly comprehensive hypoxia-related molecular landscape in tumor tissues that provided novel evidence and perspectives to explain the role of hypoxia in HCC. Clinically, the data obtained from the present study may enable the development of individualized treatment or management strategies for HCC patients with different levels of hypoxia exposure.
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影响因子：
30.8
作者：
Bhandari, Vinayak;Hoey, Christianne;Bristow, Robert G.
通讯作者：
Bristow, Robert G.
影响因子：
3.1
作者：
Sorensen, Brita Singers;Toustrup, Kasper;Alsner, Jan
通讯作者：
Alsner, Jan
DOI：
10.1158/1078-0432.ccr-13-0542
发表时间：
2013-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Eustace A;Mani N;Span PN;Irlam JJ;Taylor J;Betts GN;Denley H;Miller CJ;Homer JJ;Rojas AM;Hoskin PJ;Buffa FM;Harris AL;Kaanders JH;West CM
通讯作者：
West CM
DOI：
10.1002/hep.27923
发表时间：
2015-10
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Lu Y;Xu W;Ji J;Feng D;Sourbier C;Yang Y;Qu J;Zeng Z;Wang C;Chang X;Chen Y;Mishra A;Xu M;Lee MJ;Lee S;Trepel J;Linehan WM;Wang X;Yang Y;Neckers L
通讯作者：
Neckers L
影响因子：
3
作者：
Bader, GD;Hogue, CW
通讯作者：
Hogue, CW