Aerospace Center Hospital, Beijing, 100049, China.
Ultrasound Diagnosis Department, The First Medical Center of PLA General Hospital, Beijing, 100853, China.
BMC Cancer. 2024 Sep 30;24(1):1217. doi: 10.1186/s12885-024-12957-5.
In this study, we evaluated the molecular mechanisms of HuangQiSiJunZi Decoction (HQSJZD) for treating triple-negative breast cancer (TNBC) using network pharmacology and bioinformatics analyses.
Effective chemical components together with action targets of HQSJZD were selected based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Meanwhile, differentially expressed genes (DEGs) were extracted from TNBC sample data in The Cancer Genome Atlas (TCGA) database. Additionally, we built a protein-protein interaction (PPI) network and acquired hub genes. Gene Expression Omnibus(GEO) datasets were utilized to verify the accuracy of hub gene expression. Additionally, enrichment analyses were conducted on key genes. Furthermore, TNBC severity-related high-risk factors were screened through univariate together with multivariate Cox regressions; next, the logistic regression prediction model was built. Moreover, differential levels of 22 immune cell types in TNBC tissues compared with normal tissues were analyzed. The hub gene levels within pan-cancer and the human body were subsequently visualized and analyzed. Finally, quantitative PCR (RT-qPCR) was used to validate the correlation of the hub genes in TNBC cells.
The study predicted 256 targets of active ingredients and 1791 DEGs in TNBC, and obtained 16 hub genes against TNBC. The prognostic signature based on FOS, MMP9, and PGR was independent in predicting survival. A total of seven types of immune cells, such as CD4 + memory T cells, showed a significant difference in infiltration (p < 0.05), and immune cells were related to the hub genes. The HPA database was adopted for hub gene analyses, and as determined, FOS was highly expressed in most human organs. The results of RT-qPCR validation for the FOS hub gene were consistent with those of bioinformatic analyses.
HQSJZD might regulate the interleukin-17 and aging pathways via FOS genes to increase immune cell infiltration in TNBC tissues, and thus, may treat TNBC and improve the prognosis. The FOS genes are likely to be a new marker for TNBC.
本研究采用网络药理学和生物信息学分析方法，探讨黄芪四君子汤（HQSJZD）治疗三阴性乳腺癌（TNBC）的分子机制。
基于中药系统药理学数据库和分析平台（TCMSP），筛选 HQSJZD 的有效化学成分及其作用靶点。同时，从癌症基因组图谱（TCGA）数据库中提取 TNBC 样本数据中的差异表达基因（DEGs）。此外，构建蛋白质-蛋白质相互作用（PPI）网络并获取关键基因。利用基因表达综合数据库（GEO）数据集验证关键基因表达的准确性。此外，对关键基因进行富集分析。此外，通过单因素和多因素 Cox 回归筛选 TNBC 严重程度相关的高危因素，然后构建逻辑回归预测模型。此外，分析 TNBC 组织与正常组织之间 22 种免疫细胞类型的差异水平。随后可视化和分析关键基因在泛癌和人体中的水平。最后，采用实时定量 PCR（RT-qPCR）验证 TNBC 细胞中关键基因的相关性。
研究预测了 HQSJZD 的 256 个活性成分靶点和 TNBC 的 1791 个 DEGs，获得了 16 个针对 TNBC 的关键基因。基于 FOS、MMP9 和 PGR 的预后标志独立于预测生存。CD4+记忆 T 细胞等七种类型的免疫细胞的浸润存在显著差异（p<0.05），且免疫细胞与关键基因相关。采用人类蛋白质图谱（HPA）数据库进行关键基因分析，结果表明 FOS 在大多数人体器官中均高表达。FOS 关键基因的 RT-qPCR 验证结果与生物信息学分析结果一致。
HQSJZD 可能通过 FOS 基因调节白细胞介素-17 和衰老途径，增加 TNBC 组织中免疫细胞浸润，从而治疗 TNBC 并改善预后。FOS 基因可能成为 TNBC 的新标志物。
