Yuan Jie, Lin Minxia, Yang Shaohua, Yin Hao, Ouyang Shaoyong, Xie Hong, Tang Hongmei, Ou Xiaowei, Zeng Zhiqiang
Department of General Surgery, Foshan Clinical Medical School, Guangzhou University of Chinese Medicine, Foshan, China.
Department of General Surgery, Foshan Fosun Chancheng Hospital, Foshan, China.
Heliyon. 2024 May 11;10(10):e31137. doi: 10.1016/j.heliyon.2024.e31137. eCollection 2024 May 30.
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 in BRCA and construct a prognostic signature composed of inflammation-related genes.
The active ingredients of 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.
Forty-one active compounds were identified, and 265 therapeutic targets for 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, 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.
and 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.
乳腺癌（BRCA）在女性中较为常见，其患病率呈上升趋势。本研究应用网络药理学探讨[药物名称未给出]在BRCA中的潜在作用机制，并构建由炎症相关基因组成的预后标志物。
使用SymMap、TCMID和TCMSP平台筛选[药物名称未给出]的活性成分，并在UniProt数据库中确定分子靶点。使用Cytoscape 3.7.2建立“药物-活性化合物-潜在靶点”网络。对分子靶点进行疾病本体论、基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。使用AutoDock软件进行分子对接。从BRCA癌症基因组图谱（TCGA）数据库中获取与炎症相关的差异表达基因（DEG）。在训练队列中，应用单变量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）回归模型构建多基因标志物，随后通过Kaplan-Meier、Cox和受试者工作特征（ROC）分析进行验证。
鉴定出41种活性化合物，预测了[药物名称未给出]的265个治疗靶点。GO富集结果显示生物过程显著富集，如对外源生物刺激的反应、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途径显著富集。此外，[药物名称未给出]和芦丁被证明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。构建了包括BST2、GPR132、IL12B、IL18、IL1R1、IL2RB、IRF1等在内的16个炎症标志物，发现风险评分是BRCA患者总生存的强有力独立预后因素。16炎症标志物与多种临床特征（年龄、临床分期、T和N分类）相关，并可反映不同免疫细胞在肿瘤微环境中的免疫细胞浸润。
[药物名称未给出]被证明通过IRF1/STAT3/PD-L1途径介导BRCA细胞增殖和凋亡，16成员炎症标志物可能是预测BRCA患者预后的新型生物标志物，为临床治疗预后评估提供更准确的指导，对个体化治疗选择具有重要参考价值。
