Image1_Identification of ubiquitination-related gene classification and a novel ubiquitination-related gene signature for patients with triple-negative breast cancer.TIF

Background: Ubiquitination-related genes (URGs) are important biomarkers and therapeutic targets in cancer. However, URG prognostic prediction models have not been established in triple-negative breast cancer (TNBC) before. Our study aimed to explore the roles of URGs in TNBC.Methods: The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and the Gene Expression Omnibus (GEO) databases were used to identify URG expression patterns in TNBC. Non-negative matrix factorization (NMF) analysis was used to cluster TNBC patients. The least absolute shrinkage and selection operator (LASSO) analysis was used to construct the multi-URG signature in the training set (METABRIC). Next, we evaluated and validated the signature in the test set (GSE58812). Finally, we evaluated the immune-related characteristics to explore the mechanism.Results: We identified four clusters with significantly different immune signatures in TNBC based on URGs. Then, we developed an 11-URG signature with good performance for patients with TNBC. According to the 11-URG signature, TNBC patients can be classified into a high-risk group and a low-risk group with significantly different overall survival. The predictive ability of this 11-URG signature was favorable in the test set. Moreover, we constructed a nomogram comprising the risk score and clinicopathological characteristics with favorable predictive ability. All of the immune cells and immune-related pathways were higher in the low-risk group than in the high-risk group.Conclusion: Our study indicated URGs might interact with the immune phenotype to influence the development of TNBC, which contributes to a further understanding of molecular mechanisms and the development of novel therapeutic targets for TNBC.</p

Presentation_1_Integrated Network Pharmacology and Metabolomics Analysis of the Therapeutic Effects of Zi Dian Fang on Immune Thrombocytopenic Purpura.pdf

<p>Current hormone-based treatments for immune thrombocytopenic purpura (ITP) are associated with potentially serious adverse reactions. Zi Dian Fang (ZDF) is a multi-target Traditional Chinese Medicine (TCM) used to treat both the symptoms and root causes of ITP, with fewer side effects than hormone-based treatments. This study analysis of the therapeutic effects of ZDF on ITP from three aspects: platelet proliferation, immunoregulation, and inflammation. After detection of 52 chemical constituents of ZDF by UPLC-Q-TOF/MS, The main targets and pathways affected by ZDF were screened by network pharmacology and verified by Western blot and ELISA. Meanwhile, metabolomics analysis were applied to a mouse model of ITP to identify and screen endogenous terminal metabolites differentially regulated by ZDF. Integrated network pharmacology and metabolomics analysis of the therapeutic effects of ZDF on ITP may be as follows: ZDF counteracts ITP symptoms mainly by inhibiting Ras/MAPKs (Ras/Mitogen-activated protein kinases) pathway, and the expression of upstream protein (Ras) and downstream protein (p-ERK, p-JNK, p-p38) were inhibited, which affects the content of effect index associated with proliferation (Thrombopoietin, TPO; Granulocyte-macrophage colony stimulating factor, GM-CSF), inflammation (Tumor necrosis factor-α, TNF-α; Interleukin-6, IL-6), immune (Interleukin-2, IL-2; Interferon-gamma, IFN-γ; Interleukin-4, IL-4), so that the body’s arginine, Δ¹²-prostaglandin j2 (Δ¹²-PGJ2), 9-cis-Retinoic Acid, sphingosine-1-phosphate (S1P), oleic acid amide and other 12 endogenous metabolites significantly changes. Considering the established safety profile, the present study suggests ZDF may be a useful alternative to hormone-based therapies for the treatment of ITP.</p