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Article Abstract
Introduction And Hypothesis: The study is aimed at bioinformatically deciphering immune cell infiltration, signature genes, and their correlations in POP.
Methods: Three microarray datasets were included. Matrixes representing the uterosacral ligament were merged as a test matrix and the others representing vaginal tissues were merged as a validation matrix. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was performed to evaluate immune cell infiltration. Correlations among differential immune cells were revealed by Spearman's rank correlation. Differentially expressed genes (DEGs) were screened by both "Batch correction" and "RobustRankAggreg" methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes were conducted for functional analysis. Hub genes were identified through cytoHubba of Cytoscape, and further validated by a validation matrix and clinical samples as signature genes. Correlations of differential immune cells with signature genes were analyzed by Spearman's rank correlation.
Results: Five differential immune cells (macrophages, monocytes, regulatory T cell [Treg], type 1 T cell [Th1], and natural killer T cells [NKT]) were identified and eight pairs of immune cells had significant correlations. Screened 230 DEGs were extracellular matrix (ECM) and immune related. Eleven hub genes were initially identified and five of them (LOX, IL-6, SDC1, ICAM1, and CD38) were validated as signature genes. Significant correlations of differential immune cells with signature genes were shown in twelve pairs, especially Th1-IL6, NKT-IL6, Th1-ICAM1, macrophage-IL6, and macrophage-LOX pairs.
Conclusions: Pelvic organ prolapse could be considered immune related. Significantly infiltrated immune cells may contribute to the development of POP through close involvement with ECM- and immune-related signature genes.
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| http://dx.doi.org/10.1007/s00192-022-05378-0 | DOI Listing |
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