Ren Ning, Yu Lulin, Qian Lihui, Ye Gewei, Zhu Zhenzheng, Yu Jieru, Sun Leitao, Zhang Leyin
Hangzhou TCM Hospital of Zhejiang Chinese Medical University (Hangzhou Hospital of Traditional Chinese Medicine), Hangzhou, China.
The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
Front Oncol. 2022 Jul 6;12:817772. doi: 10.3389/fonc.2022.817772. eCollection 2022.
This meta-analysis plus network pharmacology aimed to investigate whether traditional Chinese medicine (TCM) combined with chemotherapy is associated with more beneficial efficacy data in the treatment of gynecological cancer (GC). A total of 11 randomized controlled trials (RCTs) consisting of 863 GC patients were included. Results showed a better ORR (RR: 1.42, 95% CI: 1.18-1.71; = 21.4%; 0.282), DCR (RR: 1.13, 95% CI: 1.03-1.25; = 0.0%; 0.492), PD (RR: 0.27, 95% CI: 0.11-0.65, 0.003; = 0.0%, 0.930), and QOL (SMD: 0.85, 95% CI: 0.38-1.33, 0.005) and higher proportions of CD3 T (WMD: 5.65, 95% CI: 4.23-7.08, 0.000; = 68.3%, 0.004), CD4 T (WMD: 6.97, 95% CI: 5.35-8.59, 0.000; = 83.4%, 0.000), and the CD4/CD8 T ratio (WMD: 0.32, 95% CI: 0.23-0.42, 0.000; = 78.0%, 0.000). The number of adverse events (AEs) was significantly lower in the TCM + chemotherapy group. The active components and targets of 19 high-frequency Chinese medicines obtained from the meta-analysis were screened and explored in network pharmacology analysis. Also, a regulatory network of active components and targets, a core network and key genes, a diagram of protein interaction, network topology analysis, and gene body GO function and KEGG pathway enrichment analysis were performed. A total of 120 active components were identified. NPM1 and HSPA8 are the most critical target proteins in the core network of protein interaction. HSP90AA1 is the most important target protein in the TCM group. KEGG enrichment analysis showed that it was highly significant in the lipid and atherosclerotic pathways. Therefore, moderate evidence revealed that TCM plus chemotherapy has obvious advantages over chemotherapy alone in terms of tumor responses, QOL, peripheral blood lymphocyte levels, and fewer AEs in the treatment of GC. The potential important targets and core genes were displayed.
www.crd.york.ac.uk/PROSPERO/, identifier CRD42021252500.
本荟萃分析结合网络药理学旨在研究中药联合化疗在妇科癌症（GC）治疗中是否具有更有益的疗效数据。共纳入11项随机对照试验（RCT），涉及863例GC患者。结果显示，联合治疗组的客观缓解率（ORR）更佳（RR：1.42，95%CI：1.18 - 1.71；P = 21.4%；I² = 0.282）、疾病控制率（DCR）更佳（RR：1.13，95%CI：1.03 - 1.25；P = 0.0%；I² = 0.492）、疾病进展（PD）风险更低（RR：0.27，95%CI：0.11 - 0.65，P = 0.003；I² = 0.0%，P = 0.930）、生活质量（QOL）更高（SMD：0.85，95%CI：0.38 - 1.33，P = 0.005），且CD3⁺T细胞（WMD：5.65，95%CI：4.23 - 7.08，P = 0.000；I² = 68.3%，P = 0.004）、CD4⁺T细胞（WMD：6.97，95%CI：5.35 - 8.59，P = 0.000；I² = 83.4%，P = 0.000）以及CD4⁺/CD8⁺T细胞比值（WMD：0.32，95%CI：0.23 - 0.42，P = 0.000；I² = 78.0%，P = 0.000）比例更高。中药联合化疗组的不良事件（AE）数量显著更低。从荟萃分析中筛选出19种高频中药的活性成分和靶点，并进行网络药理学分析。此外，还进行了活性成分与靶点的调控网络、核心网络和关键基因、蛋白质相互作用图、网络拓扑分析以及基因本体GO功能和KEGG通路富集分析。共鉴定出120种活性成分。NPM1和HSPA8是蛋白质相互作用核心网络中最关键的靶蛋白。HSP90AA1是中药组中最重要的靶蛋白。KEGG富集分析表明，其在脂质和动脉粥样硬化通路中具有高度显著性。因此，中等证据表明，在GC治疗中，中药联合化疗在肿瘤反应、QOL、外周血淋巴细胞水平以及更少的AE方面比单纯化疗具有明显优势。展示了潜在的重要靶点和核心基因。
