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

Zhou, Quan; Li, Hong; Wang, Jing

doi:10.1007/s00404-018-4745-1

Cited by 13 publications

(10 citation statements)

References 51 publications

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“…[29] CCL2, a cytokine involved in immunomodulatory and inflammatory processes, [30] plays a crucial role in repairing ECM after pelvic floor muscle damage caused by pregnancy and childbirth. [8] In addition, the CCL2/MCP1 signaling axis is a critical pathway for degradation of both collagen and fibrin. [31] However, increased degradation of collagen is a risk factor for POP.…”

Section: Discussionmentioning

confidence: 99%

“…POP can progress to advanced stages in women who have never given birth, whereas many women who have given birth do not experience the symptoms of POP. [6][7][8] Bioinformatic tools such as genetic engineering and gene expression profiling chips have facilitated the in-depth study of molecular mechanisms underlying the pathogenesis of POP and key genes involved in its development. Genetics may play a role in the development of POP, and racial and ethnic differences may influence the incidence of POP.…”

Section: Introductionmentioning

confidence: 99%

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Bioinformatic analysis of biological changes involved in pelvic organ prolapse

et al. 2023

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The molecular mechanisms involved in the pathogenesis of pelvic organ prolapse (POP) remain unclear. This study aimed to identify key molecules involved in the pathogenesis and progression of POP. Differentially expressed genes (DEGs) were identified based on gene expression data extracted from the GSE53868, GSE28660, and GSE12852 datasets in the gene expression omnibus database. The R software was used for data mining, and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analyses were performed to explore the biological functions of DEGs. A protein-protein interaction network (PPI) was constructed using the Search Tool for the Retrieval of Interacting Genes database, and hub genes were identified by the Cytoscape plug-in cytoHubba. In addition, the CIBERSORT algorithm was used to analyze and evaluate immune cell infiltration in POP tissues. A total of 92 upregulated DEGs were identified and subjected to enrichment analysis. Gene ontology analysis revealed that these DEGs were associated with response to hormones, positive regulation of cell death, collagen-containing extracellular matrix, and extracellular matrix. Kyoto encyclopedia of genes and genomes pathway analysis showed that the upregulated genes were mainly enriched in the phosphatidylinositol 3-kinase-AKT signaling pathway. The PPI network was structured. Nodes in the PPI network were associated with structural molecular activity and collagen-containing extracellular matrix. A total of 10 hub genes were identified, namely, CDKN1A, IL-6, PPARG, ADAMTS4, ADIPOQ, AREG, activating transcription factor 3, CCL2, CD36, and Cell death-inducing DNA fragmentation factor-like effector A. Furthermore, patients with POP were found to have a higher abundance of CD8-positive T cells in the 3 gene expression omnibus datasets. The abundance of CD8-positive T cells was negatively correlated with that of follicular helper T cells (Pearson correlation coefficient = −0.34, P < .01) or gamma delta T cells (Pearson correlation coefficient = −0.33, P < .01). But was positively correlated with that of M2 macrophages (Pearson correlation coefficient = 0.35, P < .01) and activated memory CD4 T cells (Pearson correlation coefficient = 0.34, P < .01). Altogether, PPARG, ADAMTS4, ADIPOQ, AREG, CD36, and Cell death-inducing DNA fragmentation factor-like effector A genes were discovered in the POP process for the first time, which should be intensively investigated.Abbreviations: APN = adiponectin, ATF3 = activating transcription factor 3, BC = batch correction, CCs = cellular components, CIDEA = Cell death-inducing DNA fragmentation factor-like effector A, DEGs = differentially expressed genes, ECM = extracellular matrix, GEO = gene expression omnibus, GO = gene ontology, KEGG = Kyoto encyclopedia of genes and genomes, MCODE = molecular complex detection, PI3K = phosphatidylinositol 3-kinase, POP = pelvic organ prolapse, PPI = protein-protein interaction network, RRA = robust rank aggregation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bioinformatic analysis of biological changes involved in pelvic organ prolapse

et al. 2023

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“…In mice, a POP phenotype has been associated with knockdown of fibulin 3 (EFEMP1), lysyl oxidase like 1 (LOXL1), fibulin 5 (FBLN5), and homeobox A11 (HOXA11) as summarized in a recent review on key genes and pathways for POP 81 . Of those four genes, variants at the EFEMP1 locus associate with POP in our data and, through analysis of height variants, also a variant at the LOXL1 locus; rs12440667-T (P = 3.6 × 10 −6 , OR = 0.94) ( Supplementary Data 19, Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank

et al. 2020

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Pelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P < 5 × 10 −8); seven common (minor allele frequency >5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.

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“…In addition, genome-wide association studies have determined that the presence of chromosomes 9q21, 10q24-26 and 17q25 is associated with the susceptibility of European patients with POP (57-59). However, the susceptibility loci on these chromosomes remain to be identified (60).…”

Section: Genetic Susceptibility and Popmentioning

confidence: 99%

Advances in molecular mechanisms of pelvic organ prolapse (Review)

et al. 2021

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Pelvic organ prolapse (POP) is a common gynecological benign disease occurring in middle-aged and elderly females. Its incidence increases every year. To date, the majority of studies investigating its etiology have not evaluated the underlying molecular mechanisms, which has caused substantial difficulties in the prevention, treatment and prognosis of POP. In the present narrative review, recent research studies concerning the molecular mechanisms of POP were systematically reviewed and the advances were summarized. The association between the incidence of POP and the reduction of the extracellular matrix, activation of oxidative stress, genetic susceptibility, denervation of the pelvic floor and reduction of estrogen infiltration were explored. POP is mainly associated with damage of pelvic floor muscles and connective tissue, which are directly caused by pregnancy and vaginal delivery. The majority of the molecular and genetic mutations associated with POP involve specific components of connective tissue synthesis and degradation. It is likely that macroscopic parameters, such as anatomy, lifestyle and reproductive factors, interact with microscopic parameters, such as physiology and genetics in the female pelvic floor, leading to POP. Additional research studies investigating the molecular mechanisms of POP should be performed, since they may aid public health strategies. In the present narrative review, a summary of these molecular mechanisms underlying the development of POP is provided. This included the relevant proteins and genes involved. On this basis, countermeasures were proposed. Contents

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

Cited by 13 publications

References 51 publications

Bioinformatic analysis of biological changes involved in pelvic organ prolapse

Bioinformatic analysis of biological changes involved in pelvic organ prolapse

Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank

Advances in molecular mechanisms of pelvic organ prolapse (Review)

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