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整合分析揭示茵陈草药与肝癌免疫调节之间的潜在机制。

An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma.

机构信息

Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province 510080, China.

出版信息

Biomed Res Int. 2020 Dec 29;2020:8886914. doi: 10.1155/2020/8886914. eCollection 2020.

DOI:10.1155/2020/8886914
PMID:33457419
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7785361/
Abstract

. 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. . 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. . 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. . 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.

摘要

. 中医(TCM)有大量证据支持茵陈草药在肝细胞癌(HCC)中的治疗价值,但作用机制仍需进一步研究。. 我们采用免疫基因集、模块基因、HCC 相关基因和茵陈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确定,其他三个基因集从公共数据库中获得。然后,我们进一步探讨了交集的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与枢纽基因表达相关的相关途径。最后,通过分子对接验证了活性化合物和靶基因的相互作用。. 茵陈包含 13 种活性化合物和 90 个靶基因。在构建茵陈、靶基因和 HCC 之间的网络后,BIRC5 被鉴定为枢纽基因。在生存和分期方面,高表达组和低表达组之间存在显著差异。不同的免疫亚型在 BIRC5 表达方面也存在显著差异。此外,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 呈正相关。分子对接的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。. 综上所述,我们的研究首次确定了茵陈草药、BIRC5、免疫治疗和 HCC 之间的新的潜在关联。我们推测茵陈可能通过抑制 BIRC5 靶向免疫检查点(CTLA4 和 LAG3)并激活免疫细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ac/7785361/a4a61afd8cf8/BMRI2020-8886914.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ac/7785361/fe7109ee1e78/BMRI2020-8886914.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ac/7785361/a4a61afd8cf8/BMRI2020-8886914.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ac/7785361/fe7109ee1e78/BMRI2020-8886914.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ac/7785361/8255b5fa8f1e/BMRI2020-8886914.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ac/7785361/c683f90fced7/BMRI2020-8886914.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ac/7785361/7efd94fd0da5/BMRI2020-8886914.004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ac/7785361/a4a61afd8cf8/BMRI2020-8886914.006.jpg

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