Analysis of modified Wumei pills in the treatment of colon cancer based on network pharmacology and bioinformatics
Description
In this study, we investigated the potential mechanisms by which modified Wumei pills may contribute to the treatment of colon cancer, utilizing network pharmacology and bioinformatics methodologies. Initially, we identified the effective active ingredients of modified Wumei pills and predicted their corresponding targets using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, we employed the GeneCards and Disgenet databases to filter for targets associated with colon cancer. A "drug-active ingredient-target-disease" network was constructed using the Venny platform, resulting in the identification of 112 common targets. Further analysis was conducted using Cytoscape software to create a network map, from which six major target genes were selected based on their Degree values: ADRA2B, CXCR3, CYP19A1, NR1H2, PAPPA, and PGR. A protein-protein interaction (PPI) network was generated using the String database, and the topological parameters were analyzed. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated significant enrichment of these target genes in various biological processes, cellular components, and molecular functions, as well as in signaling pathways related to colon cancer. Immunohistochemical analyses demonstrated that these genes were significantly expressed in colon cancer tissues. Receiver Operating Characteristic (ROC) curve analysis revealed that the PGR gene exhibited the strongest prognostic correlation. Additionally, differential gene expression analysis and immunoinfiltration correlation analysis further substantiated the involvement of these genes in colon cancer. Cox regression analysis elucidated the relationship between pathological stage and prognosis, as well as the correlation between CYP19A1 gene expression levels and patient outcomes. Immunochemical bar charts illustrated an increase in the number of specific immune cells in response to high expression levels of the target genes. Single-cell enrichment maps provided insights into the expression patterns of these genes across different cell types. Finally, molecular docking studies indicated that the active ingredients in modified Wumei pills demonstrated a strong binding affinity to the target proteins, particularly highlighting the strongest binding energy between Diop and CXCR3, suggesting potential therapeutic activity. This study provides a scientific foundation for the application of modified Wumei pills in the treatment of colon cancer and offers new avenues for future drug development and therapeutic strategies.