[Bioinformatic analysis of differentially expressed genes and immune cell infiltration in primary biliary cholangitis patients with poor response to ursodeoxycholic acid therapy].

Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology(2022)

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摘要
Objective To analyze the differentially expressed genes (DEGs) in patients with poor response to ursodeoxycholic acid (UDCA) therapy and to provide theoretical basis for the treatment of primary biliary cholangitis (PBC). Methods The GEO database was searched to obtain UDCA response related gene chip dataset. The DEGs were screened and the protein-protein interaction (PPI) network was constructed. The enrichment analysis of the biological function and signaling pathway of DEGs were carried out with the use of DAVID database. The CIBERSORT deconvolution algorithm was used to analyze the infiltration of 22 kinds of immune cells. Finally, Coremine database was used to predict traditional Chinese medicine (TCM) by analyzing the DEGs that were not only related to UDCA response, but also related to the immune cell infiltration. Results By analyzing the gene chips from UDCA responders and UDCA poor-responders, 99 DEGs were obtained. Biological function and signaling pathway enrichment analysis showed that the up-regulated DEGs were mainly enriched in immune response, virus infection, and PI3K/AKT signaling pathway and the down-regulated DEGs were mainly enriched in immune response, inflammatory reaction, complement cascade reaction, virus infection and systemic lupus erythematosus. The analysis of immune cell infiltration showed that naive B cells, resting memory CD4 T cells, M1 macrophages, and resting dendritic cells accounted for the most proportion. The infiltration level of γδ T cells in liver tissue of UDCA poor-responders was significantly lower than that of UDCA responders. TCM prediction using Coremine showed that Angelica Sinensis, Scutellaria baicalensis Georgi, Inula helenium L., Salvia miltiorrhiza Bunge, and Flos Magnoliae Officinalis were closely related to UDCA response and immune cell infiltration. Conclusion The DEGs those may be related to UDCA response were selected. The γδ T cells can affect the response to UDCA. TCMs like Angelica Sinensis may affect the response to UDCA by regulating immune cell infiltration.
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