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. 2023 Oct 12;9(10):e20709.
doi: 10.1016/j.heliyon.2023.e20709. eCollection 2023 Oct.

Prognostic model construction and target identification of Si-Wu-Tang against breast cancer

Zeye Zhang  1 , Zexin Zhang  2 , Jinqin Song  3 , Wenfeng Wu  2 , Yiqi Chen  2 , Jing Li  4 , Yongchen Wang  2 , Piwen Zhao  1
Affiliations

Prognostic model construction and target identification of Si-Wu-Tang against breast cancer

Zeye Zhang et al. Heliyon. .

Abstract

The targets and mechanisms of Si-Wu-Tang (SWT) against (Breast cancer) BRCA were identified and a survival model and nomogram was construted by network pharmacology, bioinformatic analysis and in vitro experiments. A total of 72 anti-breast cancer SWT targets were selected, among which eleven genes (MAOA、SQLE、CACNA2D1、GLI1、RORB、ITGB3、TACR1、NR3C2、CA3、RBP4 and PTK6) were used to construct a novel prognostic model of breast cancer. The anti-breast cancer activity of SWT was related to the modulation of the receptor tyrosine kinases signaling pathways. Moreover, two compounds, mairin and senkyunone were found to bind directly to ITGB3 and RORB proteins. Finally, mRNA and protein expression of ITGB3 and RORB was observed to be significantly down-regulated after incubation of MCF-7 cells with SWT. Overall, our results indicated that mairin and senkyunone were the key ingredients present in SWT, and ITGB3 as well as RORB proteins were the major targets affected by SWT. The prognostic model can be used to predict the outcome of BRCA patients.

Keywords: Bioinformatics analysis; Breast cancer; Network pharmacology; Si-Wu-Tang.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Workflow of the study design.
Fig. 2
Fig. 2
Identification of therapeutic targets of SWT against breast cancer. (A–B) WGCNA analysis of TCGA LUAD; (C–D) Differentially expressed analysis of TCGA LUAD; (E) Integrating the targets of SWT and DEGs.
Fig. 3
Fig. 3
Construction of prognostic model of SWT against breast cancer. (A–B) LASSO regression removed redundant factors; (C) Risk curve of scores; (D) KM survival analysis divided patients in two groups based on median of survival time; (E) ROC curve of prognostic model.
Fig. 4
Fig. 4
Construction of nomogram of SWT against breast cancer. (A) Univariate cox analysis; (B) Multivariate cox analysis; (C) Nomogram of SWT against breast cancer; (D) Fit curve of nomogram.
Fig. 5
Fig. 5
GO and KEGG functional enrichment analyses. (A) Molecular functions and pathways; (B–C) Protein interaction network of GO and KEGG.
Fig. 6
Fig. 6
Prediction of candidate compounds against breast cancer based on molecular and targets network.
Fig. 7
Fig. 7
Molecular docking. (A–B) Position and energy decomposition of NR3C2 docked with sitosterol; (C–D) Position and energy decomposition of NR3C2 docked with (3S,5R,8R,9R,10S,14S)-3,17-dihydroxy-4,4,8,10,14-pentamethyl-2,3,5,6,7,9-hexahydro-1H-cyclopenta[a]phenanthrene-15,16-dione; (E–F) Position and energy decomposition of NR3C2 docked with Mandenol; (G–H) Position and energy decomposition of NR3C2 docked with wallichilide; (I–J) Position and energy decomposition of NR3C2 docked with Stigmasterol; (K–L) Position and energy decomposition of ITGB3 docked with mairin; (M − N) Position and energy decomposition of RORB docked with senkyunone.
Fig. 8
Fig. 8
Molecular dynamic. (A) RMSD of ITGB3 docked with mairin and RORB docked with senkyunone; (B) RMSF of RORB docked with senkyunone; (C) RMSF of ITGB3 docked with mairin; (D) Heatmap of amino acid of ITGB3 docked with mairin; (E) Heatmap of amino acid of RORB docked with senkyunone; (F) Motion trail of RORB in senkyunone in different times; (G) Motion trail of ITGB3 in mairin in different times.
Fig. 9
Fig. 9
Verification of molecular targets of SWT against breast cancer in vitro experiments. (A) CCK8 assay of SWT pharmacological serum against MCF cell; (B–D) Expressed level of mRNA of RORB, ITGB3 and NR3C2 was verified by RT-PCR; (E–H) Expressed level of protein of RORB, ITGB3 and NR3C2 was verified by WB.
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