An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma.
An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma.
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DOI：
10.1155/2020/8886914
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发表时间：
2020
影响因子：
--
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Mo Z;Cao Z;Yu L;Wang Y;Li P;Lin Y;Zhang S
目标。大量的中医证据支持中药茵辰对肝细胞癌（HCC）的治疗价值，但其潜在机制仍有待研究。主要方法。采用免疫基因集、模块基因、hcc相关基因和银宸靶基因的交集进行进一步分析。模块基因通过加权基因共表达网络分析鉴定，其余3个基因集从公共数据库中获取。随后，我们进一步探讨了交集枢纽基因的临床价值和免疫调节作用。通过基因集富集分析研究hub基因表达的相关途径。最后，通过分子对接验证活性化合物与靶基因的相互作用。关键的发现。共检出13个活性化合物和90个靶基因。在构建了银辰、靶基因和HCC之间的网络后，BIRC5被确定为枢纽基因。高表达组与低表达组的生存期和分期差异有统计学意义。不同免疫亚型的BIRC5表达也存在显著差异。NK细胞和T细胞（CD4+效应记忆和CD4+记忆静息）与BIRC5表达呈负相关，而CTLA4和LAG3表达呈正相关。分子对接结果进一步验证了槲皮素- birc5相互作用具有良好的结合活性。的意义。总之，我们的研究首次发现了中药银陈、BIRC5、免疫治疗和HCC之间的一种新的潜在关联。我们推测茵辰可能通过抑制BIRC5靶向免疫检查点（CTLA4和LAG3）激活免疫细胞。
Aims. Abundant evidences in traditional Chinese medicine (TCM) supported the therapeutic value of herbal medicine Yinchen in hepatocellular carcinoma (HCC), but the underlying mechanism remains to be investigated. Main Methods. The intersection of immune gene set, module genes, HCC-associated genes, and target genes of Yinchen was employed for further analyses. The module genes were identified by weighted gene coexpression network analysis, and the other three gene sets were obtained from public databases. Subsequently, we further explored the clinical value and immunoregulation of the hub gene of intersection. The relevant pathways related to hub gene expression were investigated by gene set enrichment analysis. Finally, the interaction of active compounds and target genes was validated by molecular docking. Key Findings. Thirteen active compounds and 90 target genes of Yinchen were included. After constructing the network among Yinchen, target genes, and HCC, BIRC5 was identified as the hub gene. Significant difference was found between the high-expressed group and the low-expressed group in survival and stage. Different immune subtypes also presented significant difference in BIRC5 expression. Moreover, NK cell and T cell (CD4+ effector memory and CD4+ memory resting) were negatively correlated with BIRC5 expression, while CTLA4 and LAG3 were positively correlated. The results of molecular docking further validated a good binding activity of quercetin-BIRC5 interaction. Significance. In summary, our research identified for the first time a novel underlying association among herbal medicine Yinchen, BIRC5, immunotherapy, and HCC. We speculated that Yinchen may target the immune checkpoints (CTLA4 and LAG3) and activate the immune cells by suppressing BIRC5.
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影响因子：
81.5
作者：
Llovet, Josep M.;Zucman-Rossi, Jessica;Gores, Gregory
通讯作者：
Gores, Gregory
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
DOI：
10.1155/2014/373608
发表时间：
2014
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Chen Y;Sun BG;Zhang SJ;Chen ZX;Hardi CF;Xiang T
通讯作者：
Xiang T
传统中药茵陈中的三种新的抗乙型肝炎活性成分
影响因子：
5.4
作者：
Geng, Chang-An;Huang, Xiao-Yan;Chen, Ji-Jun
通讯作者：
Chen, Ji-Jun
DOI：
10.1155/2017/6178358
发表时间：
2017
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Guo Y;Li JX;Wang YL;Mao TY;Chen C;Xie TH;Han YF;Tan X;Han HX
通讯作者：
Han HX