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. 2020 Dec 29:2020:8886914.
doi: 10.1155/2020/8886914. eCollection 2020.

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

Zhuomao Mo  1 , Zhirui Cao  1 , Ling Yu  1 , Yongdan Wang  1 , Pan Li  1 , Youwu Lin  1 , Shijun Zhang  1
Affiliations

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

Zhuomao Mo et al. Biomed Res Int. .

Abstract

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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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
The flowchart of this study.
Figure 2
Figure 2
The Yinchen-active compounds-target genes network and KEGG signaling pathways: (a) showed the Yinchen-active compounds-target genes network; (b) showed the KEGG signaling pathways.
Figure 3
Figure 3
Identification of module and hub gene: (a) showed the volcano plot of differentially expressed analysis, (b) showed the cluster plot, (c) showed the correlation between modules and clinical parameters, (d) showed the correlation between genes and age, and (e) showed the Venn plot.
Figure 4
Figure 4
The correlation between clinical traits and BIRC5, immune and BIRC5: (a) showed the survival analysis results, (b) showed the correlation between stage and BIRC5 expression, (c) showed the correlation between immune subtypes and BIRC5 expression, (d–f) showed the correlation between immune cells and BIRC5 expression, and (g) showed the significant pathways enriched in the high-expression group.
Figure 5
Figure 5
The correlation between immune inhibitors and BIRC5 expression.
Figure 6
Figure 6
The molecular docking between BIRC5 and quercetin.
See this image and copyright information in PMC

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