Identification of key genes and pathways in pelvic organ prolapse based on gene expression profiling by bioinformatics analysis.

Abstract

The aim of this study was to elucidate the molecular mechanisms and to identify the key genes and pathways for pelvic organ prolapse (POP) using bioinformatics analysis. The microarray data for GSE53868 included 12 POP and 12 non-POP anterior vaginal wall samples. Differentially expressed genes (DEGs) were identified by GEO2R online tool. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database, and a DEG-associated protein-protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape. MCODE was used for module analysis of the PPI network. A total of 257 upregulated and 333 downregulated genes were identified. GO and KEGG pathway enrichment analyses showed that the upregulated DEGs were strongly associated with immune response, complement activation, classical pathway, phagocytosis, and recognition; the downregulated genes were mainly associated with cellular response to zinc ion, negative regulation of growth, and apoptotic process. Based on the PPI network, IL6, MYC, CCL2, ICAM1, PTGS2, SERPINE1, ATF3, CDKN1A, and CDKN2A were screened as hub genes. The four most significant sub-modules of DEGs were extracted after network module analysis. These genes were mainly associated with the negative regulation of growth and inflammatory response. The KEGG pathway enrichment analysis revealed that these genes were associated with Mineral absorption, Jak-STAT signaling pathway, cytokine-cytokine receptor interaction, and chemokine signaling pathway. These microarray data and bioinformatics analyses provide a useful method for the identification of key genes and pathways associated with POP. Moreover, some crucial DEGs, such as IL6, MYC, CCL2, ICAM1, PTGS2, SERPINE1, ATF3, CDKN1A, and CDKN2A, potentially play an important role in the development and progression of POP.