An individualized prognostic signature and multi‑omics distinction for early stage hepatocellular carcinoma patients with surgical resection.
An individualized prognostic signature and multi‑omics distinction for early stage hepatocellular carcinoma patients with surgical resection.
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手术切除的早期肝细胞癌患者的个体化预后特征和多组学区别
DOI：
10.18632/oncotarget.8212
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发表时间：
2016-04-26
期刊：
影响因子：
--
通讯作者：
Guo Z
中科院分区：
文献类型：
--
作者：
Ao L;Song X;Li X;Tong M;Guo Y;Li J;Li H;Cai H;Li M;Guan Q;Yan H;Guo Z
以前报道的预测肝癌术后复发的预后指标通常是基于预先定义的风险评分，这几乎不适用于不同实验室测量的样本。为了解决这个问题，我们使用170个I/II期HCC样本的基因表达谱，确定了由20个基因对组成的预后标记，其样本内相对表达排序（REO）可以稳健地预测HCC患者的无病生存期和总生存期。在两个独立的数据集中验证了这种基于REOs的预后特征。功能富集分析显示，高复发风险患者以细胞增殖和肿瘤微环境相关通路的激活为特征，而低复发风险患者则以多种代谢通路的激活为特征。我们使用癌症基因组图谱样本和多组学数据进一步研究了两个预后组的不同表观基因组学和基因组学特征。表观遗传学分析表明，两组预后组之间的转录差异与DNA甲基化改变显著一致。信号网络分析鉴定了几个具有表观基因组或基因组改变的关键基因（例如TP 53、MYC），其驱动HCC患者的不良预后。这些结果帮助我们了解决定肝癌患者预后的多组学机制。
Previously reported prognostic signatures for predicting the prognoses of postsurgical hepatocellular carcinoma (HCC) patients are commonly based on predefined risk scores, which are hardly applicable to samples measured by different laboratories. To solve this problem, using gene expression profiles of 170 stage I/II HCC samples, we identified a prognostic signature consisting of 20 gene pairs whose within-sample relative expression orderings (REOs) could robustly predict the disease-free survival and overall survival of HCC patients. This REOs-based prognostic signature was validated in two independent datasets. Functional enrichment analysis showed that the patients with high-risk of recurrence were characterized by the activations of pathways related to cell proliferation and tumor microenvironment, whereas the low-risk patients were characterized by the activations of various metabolism pathways. We further investigated the distinct epigenomic and genomic characteristics of the two prognostic groups using The Cancer Genome Atlas samples with multi-omics data. Epigenetic analysis showed that the transcriptional differences between the two prognostic groups were significantly concordant with DNA methylation alternations. The signaling network analysis identified several key genes (e.g. TP53, MYC) with epigenomic or genomic alternations driving poor prognoses of HCC patients. These results help us understand the multi-omics mechanisms determining the outcomes of HCC patients.
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影响因子：
4.6
作者：
Ha SY;Kim JH;Yang JW;Kim J;Kim B;Park CK
通讯作者：
Park CK
影响因子：
--
作者：
Gaballah, Hanaa Hibishy;Zakaria, Soha Said;Ismail, Saber Abdelrahman
通讯作者：
Ismail, Saber Abdelrahman
影响因子：
3.4
作者：
Cai, Lei;Han, Juan;Li, Xiaowu
通讯作者：
Li, Xiaowu
影响因子：
2.8
作者：
Eddy JA;Sung J;Geman D;Price ND
通讯作者：
Price ND
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y