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Author Spotlight: Liujunzi Decoction as a Traditional Chinese Treatment for Coloproctitis Cancer
Published on: October 13, 2023
Assessment of the targeted effect of Sijunzi decoction on the colorectal cancer microenvironment via the ESTIMATE
Jiaxin Du1, Quyuan Tao1, Ying Liu1
1School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
Objective:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Sijunzi decoction (SJZD) impacts colorectal cancer (CRC) by targeting core genes like HSPB1 and TGFB1. These targets influence tumor microenvironment, affecting CRC prognosis and development.
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Colorectal cancer (CRC) remains a significant health challenge.
- Traditional Chinese Medicine (TCM) offers potential adjuvant therapies for CRC.
- Understanding the molecular mechanisms of TCM in CRC is crucial for effective treatment.
Purpose of the Study:
- To investigate the therapeutic targets and pathways of Sijunzi decoction (SJZD) in the colorectal cancer (CRC) tumor microenvironment.
- To utilize network pharmacology and the ESTIMATE algorithm to elucidate SJZD's action mechanisms.
- To identify key genes and pathways modulated by SJZD in CRC.
Main Methods:
- Employed the ESTIMATE algorithm to assess immune and stromal cell infiltration in CRC.
- Searched active SJZD components and targets in TCM databases (TCMSP, UniProt).
- Integrated CRC gene expression data with SJZD targets to identify core genes, followed by GO, KEGG enrichment, and TCGA validation.
Main Results:
- Low stromal score correlated with significantly longer survival in CRC patients (P = 0.018).
- Identified 139 SJZD active components and 52 targets, with HSPB1, SPP1, IGFBP3, and TGFB1 as core targets.
- Core targets were linked to poor prognosis in TCGA data and enriched in hypoxia response, extracellular matrix interactions, and TNF signaling pathways.
Conclusions:
- The core genes (HSPB1, SPP1, IGFBP3, TGFB1) significantly influence colorectal cancer (CRC) progression and prognosis.
- These genes modulate CRC development by regulating hypoxia, protein binding, and epithelial-mesenchymal transition within the extracellular matrix.
- SJZD shows therapeutic potential against CRC by targeting these key molecular pathways.
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