School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.
PLoS One. 2022 Mar 18;17(3):e0264720. doi: 10.1371/journal.pone.0264720. eCollection 2022.
Sijunzi decoction (SJZD) was used to treat patients with colorectal cancer (CRC) as an adjuvant method. The aim of the study was to investigate the therapeutic targets and pathways of SJZD towards the tumor microenvironment of CRC via network pharmacology and the ESTIMATE algorithm.
The ESTIMATE algorithm was used to calculate immune and stromal scores to predict the level of infiltrating immune and stromal cells. The active targets of SJZD were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and UniProt database. The core targets were obtained by matching the differentially expressed genes in CRC tissues and the targets of SJZD. Then, GO, KEGG and validation in TCGA were carried out.
According to the ESTIMATE algorithm and survival analysis, the median survival time of the low stromal score group was significantly higher than that of the high stromal score group (P = 0.018), while the patients showed no significant difference of OS between different immune groups (P = 0.19). A total of 929 genes were upregulated and 115 genes were downregulated between the stromal score groups (|logFC| > 2, adjusted P < 0.05); 357 genes were upregulated and 472 genes were downregulated between the immune score groups. The component-target network included 139 active components and 52 related targets. The core targets were HSPB1, SPP1, IGFBP3, and TGFB1, which were significantly associated with poor prognosis in TCGA validation. GO terms included the response to hypoxia, the extracellular space, protein binding and the TNF signaling pathway. Immunoreaction was the main enriched pathway identified by KEGG analysis.
The core genes (HSPB1, SPP1, IGFBP3 and TGFB1) affected CRC development and prognosis by regulating hypoxia, protein binding and epithelial-mesenchymal transition in the extracellular matrix.
四君子汤（SJZD）被用作治疗结直肠癌（CRC）患者的辅助方法。本研究旨在通过网络药理学和 ESTIMATE 算法探讨 SJZD 对 CRC 肿瘤微环境的治疗靶点和途径。
采用 ESTIMATE 算法计算免疫和基质评分，以预测浸润免疫和基质细胞的水平。在中药系统药理学数据库和分析平台（TCMSP）和 UniProt 数据库中搜索 SJZD 的活性靶标。通过匹配 CRC 组织中的差异表达基因和 SJZD 的靶标，获得核心靶标。然后进行 GO、KEGG 和 TCGA 验证。
根据 ESTIMATE 算法和生存分析，低基质评分组的中位生存时间明显高于高基质评分组（P = 0.018），而不同免疫组间的 OS 无显著差异（P = 0.19）。基质评分组间共有 929 个基因上调，115 个基因下调（|logFC|＞2，调整 P＜0.05）；免疫评分组间有 357 个基因上调，472 个基因下调。成分-靶标网络包括 139 个活性成分和 52 个相关靶标。核心靶标为 HSPB1、SPP1、IGFBP3 和 TGFB1，在 TCGA 验证中与预后不良显著相关。GO 术语包括对缺氧的反应、细胞外空间、蛋白结合和 TNF 信号通路。KEGG 分析主要富集途径为免疫反应。
核心基因（HSPB1、SPP1、IGFBP3 和 TGFB1）通过调节细胞外基质中的缺氧、蛋白结合和上皮-间充质转化，影响 CRC 的发生发展和预后。
