PDF(Pubmed)
Abstract：
UNASSIGNED: The prevalence of breast cancer (BRCA), which is common among women, is on the rise. This study applied network pharmacology to explore the potential mechanism of action of herba sarcandrae in BRCA and construct a prognostic signature composed of inflammation-related genes.
UNASSIGNED: The active ingredients of herba sarcandrae were screened using the SymMap, TCMID, and TCMSP platforms, and the molecular targets were determined in the UniProt database. The \"drug-active compound-potential target\" network was established with Cytoscape 3.7.2. The molecular targets were subjected to disease ontology, gene ontology (GO), and Kyoto Encyclopedia of Genes (KEGG) analyses. AutoDock software was used for molecular docking. Differentially expressed genes (DEGs) related to inflammation were obtained from the BRCA Cancer Genome Atlas (TCGA) database. In the training cohort, the univariate Cox regression model was applied to preliminarily screen prognostic genes. A multigene signature was built by the least absolute shrinkage and selection operator (LASSO) regression model, followed by validation through Kaplan‒Meier, Cox, and receiver operating characteristic (ROC) analyses.
UNASSIGNED: Forty-one active compounds were identified, and 265 therapeutic targets for herba sarcandrae were predicted. GO enrichment results revealed significant enrichment of biological processes, such as response to xenobiotic stimuli, response to nutrient levels, and response to lipopolysaccharide. KEGG analysis revealed significant enrichment of pathways such as AGE-RAGE and chemical carcinogenesis receptor activation signaling pathways. In addition, the herbs Marc-Andre and rutin were shown to mediate BRCA cell proliferation and apoptosis via the interferon regulatory factor 1 (IRF1)/signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) pathway. Sixteen inflammatory signatures, including BST2, GPR132, IL12B, IL18, IL1R1, IL2RB, IRF1, and others, were constructed, and the risk score was found to be a strong independent prognostic factor for overall survival in BRCA patients. The 16-inflammation signature was associated with several clinical features (age, clinical stage, T, and N classifications) and could reflect immune cell infiltration in tumor microenvironments with different immune cells.
UNASSIGNED: Herba sarcandrae and rutin were shown to mediate BRCA cell proliferation and apoptosis via the IRF1/STAT3/PD-L1 pathway, and the 16-member inflammatory signature might be a novel biomarker for predicting BRCA patient prognosis, providing more accurate guidance for clinical treatment prognosis evaluation and having important reference value for individualized treatment selection.
UNASSIGNED: The active ingredients of herba sarcandrae were screened using the SymMap, TCMID, and TCMSP platforms, and the molecular targets were determined in the UniProt database. The \"drug-active compound-potential target\" network was established with Cytoscape 3.7.2. The molecular targets were subjected to disease ontology, gene ontology (GO), and Kyoto Encyclopedia of Genes (KEGG) analyses. AutoDock software was used for molecular docking. Differentially expressed genes (DEGs) related to inflammation were obtained from the BRCA Cancer Genome Atlas (TCGA) database. In the training cohort, the univariate Cox regression model was applied to preliminarily screen prognostic genes. A multigene signature was built by the least absolute shrinkage and selection operator (LASSO) regression model, followed by validation through Kaplan‒Meier, Cox, and receiver operating characteristic (ROC) analyses.
UNASSIGNED: Forty-one active compounds were identified, and 265 therapeutic targets for herba sarcandrae were predicted. GO enrichment results revealed significant enrichment of biological processes, such as response to xenobiotic stimuli, response to nutrient levels, and response to lipopolysaccharide. KEGG analysis revealed significant enrichment of pathways such as AGE-RAGE and chemical carcinogenesis receptor activation signaling pathways. In addition, the herbs Marc-Andre and rutin were shown to mediate BRCA cell proliferation and apoptosis via the interferon regulatory factor 1 (IRF1)/signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) pathway. Sixteen inflammatory signatures, including BST2, GPR132, IL12B, IL18, IL1R1, IL2RB, IRF1, and others, were constructed, and the risk score was found to be a strong independent prognostic factor for overall survival in BRCA patients. The 16-inflammation signature was associated with several clinical features (age, clinical stage, T, and N classifications) and could reflect immune cell infiltration in tumor microenvironments with different immune cells.
UNASSIGNED: Herba sarcandrae and rutin were shown to mediate BRCA cell proliferation and apoptosis via the IRF1/STAT3/PD-L1 pathway, and the 16-member inflammatory signature might be a novel biomarker for predicting BRCA patient prognosis, providing more accurate guidance for clinical treatment prognosis evaluation and having important reference value for individualized treatment selection.
摘要：
■乳腺癌（BRCA）的患病率，这在女性中很常见，正在上升。本研究应用网络药理学探讨了sarcandrae在BRCA中的潜在作用机制，并构建了由炎症相关基因组成的预后标志。
■使用SymMap筛选了sarcandrae的活性成分，TCMID,和TCMSP平台，并在UniProt数据库中确定分子靶标。使用Cytoscape3.7.2建立了“药物活性化合物潜在目标”网络。分子靶标受到疾病本体论，基因本体论(GO)，和京都基因百科全书(KEGG)分析。AutoDock软件用于分子对接。从BRCA癌症基因组图谱(TCGA)数据库获得与炎症相关的差异表达基因(DEGs)。在训练组中，应用单因素Cox回归模型初步筛选预后基因。通过最小绝对收缩和选择算子(LASSO)回归模型建立多基因签名，然后通过卡普兰·迈耶进行验证，考克斯,和接收器工作特性(ROC)分析。
■确定了41种活性化合物，并预测了265个苦参的治疗靶标。GO富集结果揭示了生物过程的显著富集，例如对异生刺激的反应，对营养水平的反应，和对脂多糖的反应。KEGG分析显示，AGE-RAGE和化学致癌受体激活信号通路等通路显着富集。此外,研究表明,中药Marc-Andre和芦丁通过干扰素调节因子1(IRF1)/信号转导和转录激活因子3(STAT3)/程序性死亡-配体1(PD-L1)途径介导BRCA细胞增殖和凋亡.十六个炎症特征，包括BST2,GPR132,IL12B,IL18,IL1R1,IL2RB,IRF1和其他人，被建造，并且发现风险评分是BRCA患者总生存期的重要独立预后因素.16-炎症特征与几个临床特征(年龄，临床分期,T,和N分类），可以反映具有不同免疫细胞的肿瘤微环境中的免疫细胞浸润。
■虫草和芦丁通过IRF1/STAT3/PD-L1通路介导BRCA细胞增殖和凋亡，16个成员的炎症特征可能是预测BRCA患者预后的新生物标志物，为临床治疗预后评估提供更准确的指导,对个体化治疗方案选择具有重要的参考价值。
■使用SymMap筛选了sarcandrae的活性成分，TCMID,和TCMSP平台，并在UniProt数据库中确定分子靶标。使用Cytoscape3.7.2建立了“药物活性化合物潜在目标”网络。分子靶标受到疾病本体论，基因本体论(GO)，和京都基因百科全书(KEGG)分析。AutoDock软件用于分子对接。从BRCA癌症基因组图谱(TCGA)数据库获得与炎症相关的差异表达基因(DEGs)。在训练组中，应用单因素Cox回归模型初步筛选预后基因。通过最小绝对收缩和选择算子(LASSO)回归模型建立多基因签名，然后通过卡普兰·迈耶进行验证，考克斯,和接收器工作特性(ROC)分析。
■确定了41种活性化合物，并预测了265个苦参的治疗靶标。GO富集结果揭示了生物过程的显著富集，例如对异生刺激的反应，对营养水平的反应，和对脂多糖的反应。KEGG分析显示，AGE-RAGE和化学致癌受体激活信号通路等通路显着富集。此外,研究表明,中药Marc-Andre和芦丁通过干扰素调节因子1(IRF1)/信号转导和转录激活因子3(STAT3)/程序性死亡-配体1(PD-L1)途径介导BRCA细胞增殖和凋亡.十六个炎症特征，包括BST2,GPR132,IL12B,IL18,IL1R1,IL2RB,IRF1和其他人，被建造，并且发现风险评分是BRCA患者总生存期的重要独立预后因素.16-炎症特征与几个临床特征(年龄，临床分期,T,和N分类），可以反映具有不同免疫细胞的肿瘤微环境中的免疫细胞浸润。
■虫草和芦丁通过IRF1/STAT3/PD-L1通路介导BRCA细胞增殖和凋亡，16个成员的炎症特征可能是预测BRCA患者预后的新生物标志物，为临床治疗预后评估提供更准确的指导,对个体化治疗方案选择具有重要的参考价值。
