Bioinformatics predictions of immune mechanism and traditional Chinese medicine of intrauterine growth restriction.

Objective: Based on bioinformatics technology, gene set enrichment analysis (GSEA) and immune infiltration analysis of key differential genes were performed on the chip data of intrauterine growth restriction (IUGR), and the related effects of traditional Chinese medicine were predicted. Methods: GSE12216 chip data were obtained from Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) were screened by the R software. Then, Gene Set Enrichment Analysis (GSEA) was used to analyze gene ontology (GO) functional and Kyoto encyclopedia of genes and genome (KEGG) for all expression data, and GO and KEGG of DEGs were analyzed by the R-package. The DEGs protein interaction network was constructed by STRING database, and the key genes were screened by Cytohubba; ROC analysis of key genes to judge the diagnostic value of key genes; contents and proportion of 24 immune cells in IUGR were obtained by single sample gene set enrichment analysis (ssGSEA); the correlation between key gene expression and immune cell infiltration was calculated by Spearman statistical analysis, and the immune related key genes were predicted by Coremine database. Results: Total 228 IUGR and DEGs of normal placenta were obtained; GSEA results showed that the gene expression changes of IUGR samples were mainly related to chemokines, receptors and lysosomal signal pathway; GO and KEGG analysis of DEGs showed that DEGs were mainly enriched in TNF signaling pathway, HIF-1 signaling pathway and JAK/STAT signaling pathway; Cytohubba screened 10 key genes: CSF2, IRAK1, PTGS2, FLT1, CHUK, CXCL12, FOS, LEP, CXCL2 and RELB; ROC analysis showed that these 10 genes had high diagnostic value; infiltration matrix analysis of immune cells revealed that natural killer T cells (NKTs) and monocytes appeared significantly altered in IUGR placentas. The correlation analysis between immune infiltration and key genes found that seven genes CSF2, IRAK1, PTGS2, CHUK, CXCL12, CXCL2 and RELB were correlated with immune infiltration. According to the prediction of traditional Chinese medicine, it was found that ginseng and Astragalus had the closest relationship with IUGR related immune infiltration. Conclusion: NKT cells and monocytes play an important role in the development and occurrence of IUGR; we identified seven genes that are involved with immune infiltration; Ginseng and Scutellaria baicalensis can be used as drug sources for the treatment of IUGR. [ABSTRACT FROM AUTHOR]