Co-expression network analysis identified six hub genes in association with metastasis risk and prognosis in hepatocellular carcinoma.
Co-expression network analysis identified six hub genes in association with metastasis risk and prognosis in hepatocellular carcinoma.
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共表达网络分析确定了六个枢纽基因与肝细胞癌的转移风险和预后相关。
DOI：
10.18632/oncotarget.16896
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发表时间：
2017-07-25
期刊：
影响因子：
--
通讯作者：
Zhao Q
中科院分区：
文献类型：
--
作者：
Chen P;Wang F;Feng J;Zhou R;Chang Y;Liu J;Zhao Q
肝细胞癌（HCC）是世界范围内发病率和死亡率较高的肿瘤，其发生和发展受到复杂的基因相互作用网络的影响。构建加权基因共表达网络，以识别与HCC临床特征相关的基因模块（n = 214）。在13个模块中，仅在红色模块和转移风险（根据HCC转移基因特征分类）之间发现了高相关性（R2 =-0.74）。此外，在红色模块中，确定了34个转移风险网络枢纽基因，其中6个（ABAT、AGXT、ALDH 6A 1、CYP 4A 11、DAO和EHHADH）也是模块基因的蛋白质-蛋白质相互作用网络中的枢纽节点。因此，总共鉴定了六个枢纽基因。在验证中，在测试集中，所有枢纽基因显示与四阶段HCC进展负相关（趋势P < 0.05）。此外，在训练集中，具有低表达的任何枢纽基因的HCC样品显示出较高的复发率和较差的存活率（95%置信区间的风险比> 1）。142例HCC样本的RNA测序数据显示预后结果一致。基因集富集分析（Gene set enrichment analysis，GSEA）结果表明，在所有hub基因高表达的样品中，共有24个功能基因集被富集，其中大部分集中在氨基酸代谢和氧化方面。结论：共表达网络分析发现6个与肝癌转移风险和预后相关的hub基因，它们可能通过影响氨基酸代谢和氧化而改善预后。
Hepatocellular carcinoma (HCC) has a high incidence and mortality worldwide, and its carcinogenesis and progression are influenced by a complex network of gene interactions. A weighted gene co-expression network was constructed to identify gene modules associated with the clinical traits in HCC (n = 214). Among the 13 modules, high correlation was only found between the red module and metastasis risk (classified by the HCC metastasis gene signature) (R2 = −0.74). Moreover, in the red module, 34 network hub genes for metastasis risk were identified, six of which (ABAT, AGXT, ALDH6A1, CYP4A11, DAO and EHHADH) were also hub nodes in the protein-protein interaction network of the module genes. Thus, a total of six hub genes were identified. In validation, all hub genes showed a negative correlation with the four-stage HCC progression (P for trend < 0.05) in the test set. Furthermore, in the training set, HCC samples with any hub gene lowly expressed demonstrated a higher recurrence rate and poorer survival rate (hazard ratios with 95% confidence intervals > 1). RNA-sequencing data of 142 HCC samples showed consistent results in the prognosis. Gene set enrichment analysis (GSEA) demonstrated that in the samples with any hub gene highly expressed, a total of 24 functional gene sets were enriched, most of which focused on amino acid metabolism and oxidation. In conclusion, co-expression network analysis identified six hub genes in association with HCC metastasis risk and prognosis, which might improve the prognosis by influencing amino acid metabolism and oxidation.
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