Bioinformatically deciphering immune cell infiltration and signature genes in pelvic organ prolapse

Wu, Chenghao; Zhou, Zixuan; Yang, Yuanyuan; Li, Huaifang; Guo, Yi; Tong, Xiaowen

doi:10.1007/s00192-022-05378-0

Cited by 8 publications

(5 citation statements)

References 23 publications

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“…As mentioned above, we observed enriched pathways including "Interleukin-10 signaling", "regulation of leukocyte proliferation", "lipid and atherosclerosis pathway", and "regulation of mononuclear cell proliferation". A recent MR study identi ed an inverse causal relationship between HDL cholesterol (HDL-C) levels and POP, corroborating the results of prior observational studies [22,33]. Our study revealed a noteworthy positive causal relationship between IL10 signaling molecules and POP, despite IL10's primary role as an anti-in ammatory cytokine that safeguards the body from excessive immune responses.…”

Section: Discussionsupporting

confidence: 88%

Circulating Inflammatory Biomarkers mediates the causal effect of Aging on Female Pelvic Organ Prolapse: Mendelian Randomization Analysis

Huang,

Xiao,

Chen

et al. 2024

Preprint

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Aims Female pelvic organ prolapse (POP) is a disease associated with aging and inflammation, though it is not determined that aging and inflammation are causative factors. The purpose of this study was to evaluate the causal effects of aging and inflammatory factors on female pelvic organ prolapse (POP). Methods Significant genetic variables were evaluated by assessing genome-wide association study (GWAS) data for POP and 5 age biomarkers (GrimAge, HorvathAge, HannumAge, PhenoAge, and leukocyte telomere length). Initially, a bidirectional MR analysis was conducted utilizing a random-effects inverse variance-weighted IVW method to elucidate the causal association. Other MR methods and sensitivity analyses were also used. Then, we also used a two-step MR analysis to analyze the mediating effect of six circulating inflammatory biomarkers in the causal relationship between age and POP. Finally, two-sample MR analysis was also used to investigate the effects of 190 inflammatory cytokines on POP risk. Results Shorter leukocyte telomere length (LTL), rather than epigenetic clocks is genetically predicted to increase the risk of POP. MR analysis showed that shorter LTL is associated with higher leukocyte count, which can lead to POP. A significant causal association was found between 44 circulating inflammatory cytokines and POP risk. After adjusting for multiple tests, CXCL14, IL17A, IL18, IL6, TNFRSF10B, and TNFSF9 remained statistically significant. Conclusions Our findings provide that leukocyte count mediates the potential genetic causal impact of shorter LTL on the development of POP. Inflammatory cytokines might to be considered as potential targets for intervention in POP.

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Section: Discussionsupporting

confidence: 88%

Circulating Inflammatory Biomarkers mediates the causal effect of Aging on Female Pelvic Organ Prolapse: Mendelian Randomization Analysis

Huang,

Xiao,

Chen

et al. 2024

Preprint

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“…CD8 + T cells are overactivated in the specific inflammatory microenvironment of POP and can kill the corresponding functional cells. [46] However, this study has some limitations. First, the limited number of patients with POP may have led to bias.…”

Section: Discussionmentioning

confidence: 89%

“…CD8 + T cells are overactivated in the specific inflammatory microenvironment of POP and can kill the corresponding functional cells. [46]…”

Section: Discussionmentioning

confidence: 99%

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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“…Simultaneously, GO analysis showed that mast cells were signi cantly downregulated in pathways such as ECM organization, indicating that mast cells may play crucial roles in the regulation of ECM in the USL. Collectively, we propose that the ECM interacts with the immune system, possibly causing the accumulation and remodeling of the ECM, and the accumulation of ECM leads to the proliferation of immune cells, leading to a sustained in ammatory response 51,52 .…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis of uterosacral ligament revealed cellular heterogeneity in women with pelvic organ prolapse

Liu

Sue²,

Wei³

et al. 2023

Preprint

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Pelvic organ prolapse (POP) markedly affects the quality of life of women, including significant financial burden. Different cell types and corresponding marker genes were identified in the vaginal wall of women with POP; however, no study has explored gene expression and cellular heterogeneity in the uterosacral ligament. Using single-cell RNA sequencing, we constructed a transcriptional profile of the uterosacral ligament and control samples, and identified 10 major cell types. We performed subpopulation analysis of POP primary cells, explored differentially expressed genes, and performed pseudo-time and transcription factor analyses. We verified previous cell clusters of human fibroblasts, neutrophils, and found new clusters of uterosacral ligaments. Additionally, we dissected pattern changes of cell–cell interaction between stromal and immune cells and transcription factors related to the extracellular matrix, development, and immunity in POP. Here we provide insight into the molecular mechanisms of POP and valuable information for future research directions.

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Bioinformatically deciphering immune cell infiltration and signature genes in pelvic organ prolapse

Cited by 8 publications

References 23 publications

Circulating Inflammatory Biomarkers mediates the causal effect of Aging on Female Pelvic Organ Prolapse: Mendelian Randomization Analysis

Circulating Inflammatory Biomarkers mediates the causal effect of Aging on Female Pelvic Organ Prolapse: Mendelian Randomization Analysis

Bioinformatic analysis of biological changes involved in pelvic organ prolapse

Single-cell analysis of uterosacral ligament revealed cellular heterogeneity in women with pelvic organ prolapse

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