Effects of PKM2 on global metabolic changes and prognosis in hepatocellular carcinoma: from gene expression to drug discovery.
Effects of PKM2 on global metabolic changes and prognosis in hepatocellular carcinoma: from gene expression to drug discovery.
复制标题
PKM2 对肝细胞癌整体代谢变化和预后的影响：从基因表达到药物发现
DOI：
10.1186/s12885-018-5023-0
复制
发表时间：
2018-11-21
期刊：
影响因子：
3.8
通讯作者：
Li WX
中科院分区：
文献类型：
--
作者：
Lv WW;Liu D;Liu XC;Feng TN;Li L;Qian BY;Li WX
研究背景肝细胞癌（HCC）是威胁全球人类健康的恶性肿瘤。 PKM2 高表达在多种癌症中被广泛报道，尤其是在 HCC 中。本研究旨在探讨PKM2对整体基因表达、代谢损伤、患者预后和多重转录调控关系的影响，以及鉴定几个关键代谢基因并筛选一些小分子药物。方法转录组和临床HCC数据从NIH-GDC存储库下载。有关代谢基因和子系统的信息是从 Recon 2 人类代谢模型中收集的。药物-蛋白质相互作用数据从 DrugBank 和 UniProt 数据库获得。我们将PKM2表达水平≥11.25的患者定义为高PKM2组，将PKM2低表达（< 11.25）的患者定义为低PKM2组。结果结果显示，整体代谢基因表达水平明显分为高PKM2组和低PKM2组。此外，在高 PKM2 组中观察到更多受影响的代谢子系统。此外，我们还发现了 98 个 PKM2 相关失调代谢基因，这些基因与患者总体生存率较差相关。总之，这些发现表明 PKM2 对 HCC 具有更全面的影响。此外，我们筛选了几种针对这些代谢酶的小分子药物，其中一些已用于抗肿瘤临床研究。结论PKM2高表达的HCC患者比PKM2低表达的个体表现出更严重的代谢损伤、转录调控失衡和较差的预后。我们相信我们的研究为 HCC 的病理学研究和药物开发提供了有价值的信息。
BackgroundHepatocellular carcinoma (HCC) is a malignant tumor that threatens global human health. High PKM2 expression is widely reported in multiple cancers, especially in HCC. This study aimed to explore the effects of PKM2 on global gene expression, metabolic damages, patient prognosis, and multiple transcriptional regulation relationships, as well as to identify several key metabolic genes and screen some small-molecule drugs.MethodsTranscriptome and clinical HCC data were downloaded from the NIH-GDC repository. Information regarding the metabolic genes and subsystems was collected from the Recon 2 human metabolic model. Drug-protein interaction data were obtained from the DrugBank and UniProt databases. We defined patients with PKM2 expression levels ≥11.25 as the high-PKM2 group, and those with low PKM2 expression (< 11.25) were defined as the low-PKM2 group.ResultsThe results showed that the global metabolic gene expression levels were obviously divided into the high- or low-PKM2 groups. In addition, a greater number of affected metabolic subsystems were observed in the high-PKM2 group. Furthermore, we identified 98 PKM2-correlated deregulated metabolic genes that were associated with poor overall patient survival. Together, these findings suggest more comprehensive influences of PKM2 on HCC. In addition, we screened several small-molecule drugs that target these metabolic enzymes, some of which have been used in antitumor clinical studies.ConclusionsHCC patients with high PKM2 expression showed more severe metabolic damage, transcriptional regulation imbalance and poor prognosis than low-PKM2 individuals. We believe that our study provides valuable information for pathology research and drug development for HCC.
登录
查看更多内容
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
4.6
作者：
Han H;Shim H;Shin D;Shim JE;Ko Y;Shin J;Kim H;Cho A;Kim E;Lee T;Kim H;Kim K;Yang S;Bae D;Yun A;Kim S;Kim CY;Cho HJ;Kang B;Shin S;Lee I
通讯作者：
Lee I
DOI：
10.1126/science.1211485
发表时间：
2011-12-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Anastasiou D;Poulogiannis G;Asara JM;Boxer MB;Jiang JK;Shen M;Bellinger G;Sasaki AT;Locasale JW;Auld DS;Thomas CJ;Vander Heiden MG;Cantley LC
通讯作者：
Cantley LC
DAPK1 作为肝癌的独立预后标志物。
影响因子：
2.7
作者：
Li L;Guo L;Wang Q;Liu X;Zeng Y;Wen Q;Zhang S;Kwok HF;Lin Y;Liu J
通讯作者：
Liu J
影响因子：
--
作者：
Hu W;Lu SX;Li M;Zhang C;Liu LL;Fu J;Jin JT;Luo RZ;Zhang CZ;Yun JP
通讯作者：
Yun JP