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. 2017 Aug 9;7(1):7668.
doi: 10.1038/s41598-017-08185-6.

Expression Changes in Pelvic Organ Prolapse: A Systematic Review and in Silico Study

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Free PMC article

Expression Changes in Pelvic Organ Prolapse: A Systematic Review and in Silico Study

Maryam B Khadzhieva et al. Sci Rep. .
Free PMC article

Abstract

Pelvic organ prolapse (POP) is a highly disabling condition common for a vast number of women worldwide. To contribute to existing knowledge in POP pathogenesis, we performed a systematic review of expression studies on both specific gene and whole-genome/proteome levels and an in silico analysis of publicly available datasets related to POP development. The most extensively investigated genes in individual studies were related to extracellular matrix (ECM) organization. Three premenopausal and two postmenopausal sets from two Gene Expression Omnibus (GEO) studies (GSE53868 and GSE12852) were analyzed; Gene Ontology (GO) terms related to tissue repair (locomotion, biological adhesion, immune processes and other) were enriched in all five datasets. Co-expression was higher in cases than in controls in three premenopausal sets. The shared between two or more datasets up-regulated genes were enriched with those related to inflammatory bowel disease (IBD) in the NHGRI GWAS Catalog. ECM-related genes were not over-represented among differently expressed genes. Up-regulation of genes related to tissue renewal probably reflects compensatory mechanisms aimed at repair of damaged tissue. Inefficiency of this process may have different origins including age-related deregulation of gene expression.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Summary of literature data on POP-related expression changes for selected genes. Numbers in boxes indicate the number of studies (Fig. 1a) and subjects (Fig. 1b) for each marker. Letter symbols (a–g) in the small boxes are decrypted in the right upper corner.
Figure 2
Figure 2
(a) Heat map for GO terms cluster representatives for genes considered in POP studies. (b) GO terms associated with the selected genes. Color indicates the user-supplied P- value; the term ‘frequency’ means frequency of the specific term in the underlying GO annotation database.
Figure 3
Figure 3
Graph for the results of enrichment analysis for five gene sets up-regulated in POP. More similar nodes are placed closer together. The line width indicates the degree of similarity between GO terms cluster representatives. Clustering by color into super clusters was obtained by using REVIGO TreeMap application.
Figure 4
Figure 4
Co-expression heatmaps and density plots. Heatmaps display Pearson correlation coefficients for gene expression in controls (above the diagonal) and cases (below the diagonal). Density plots present correlation coefficients distribution for controls (blue) and cases (red) with addition of percentage of Pearson correlations (r-values) ≥ 0.7 and ≤ -0.7. Density plots x-axis: Pearson correlation coefficient (r), y-axis: density.
Figure 5
Figure 5
REVIGO scatterplot for GO terms cluster representatives for shared genes up-regulated in POP tissues. Bubble color indicates the user-supplied P - value; size shows the frequency of the GO term in the GO annotation database.

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