Bioinformatics searching of diagnostic markers and immune infiltration in polycystic ovary syndrome

Yao, Xinrui; Wang, Xiuxia

doi:10.3389/fgene.2022.937309

Cited by 8 publications

(6 citation statements)

References 70 publications

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“…IL1R1 imbalance in ectopic endometrial tissue of women suffering from / with endometriosis results in heightened sensitivity to IL1 stimulation, which affects their ability to develop into host tissues for implantation ( 55 ). HMOX1 dysregulation has been implicated in PCOS ( 56 ), endometriosis ( 57 ), and in-vitro is down-regulated in endometrial stromal fibroblasts obtained from healthy patients in late secretory phase ( 58 ). Finally, PCOS patients exhibit significant differences in their immune cell population distribution and associated cytokine production, and display defective vascular remodelling of the endometrium ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

Homeobox regulator Wilms Tumour 1 is displaced by androgen receptor at cis-regulatory elements in the endometrium of PCOS patients

James,

Quintela,

Lucini

et al. 2024

Front. Endocrinol.

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Decidualisation, the process whereby endometrial stromal cells undergo morphological and functional transformation in preparation for trophoblast invasion, is often disrupted in women with polycystic ovary syndrome (PCOS) resulting in complications with pregnancy and/or infertility. The transcription factor Wilms tumour suppressor 1 (WT1) is a key regulator of the decidualization process, which is reduced in patients with PCOS, a complex condition characterized by increased expression of androgen receptor in endometrial cells and high presence of circulating androgens. Using genome-wide chromatin immunoprecipitation approaches on primary human endometrial stromal cells, we identify key genes regulated by WT1 during decidualization, including homeobox transcription factors which are important for regulating cell differentiation. Furthermore, we found that AR in PCOS patients binds to the same DNA regions as WT1 in samples from healthy endometrium, suggesting dysregulation of genes important to decidualisation pathways in PCOS endometrium due to competitive binding between WT1 and AR. Integrating RNA-seq and H3K4me3 and H3K27ac ChIP-seq metadata with our WT1/AR data, we identified a number of key genes involved in immune response and angiogenesis pathways that are dysregulated in PCOS patients. This is likely due to epigenetic alterations at distal enhancer regions allowing AR to recruit cofactors such as MAGEA11, and demonstrates the consequences of AR disruption of WT1 in PCOS endometrium.

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Section: Discussionmentioning

confidence: 99%

Homeobox regulator Wilms Tumour 1 is displaced by androgen receptor at cis-regulatory elements in the endometrium of PCOS patients

James,

Quintela,

Lucini

et al. 2024

Front. Endocrinol.

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“…Moreover, high levels of ROS and immunoinflammatory factors could increase the expression of RIPK1 and RIPK3 in GCs ( 15 ). Furthermore, dysregulation of GCs and immune cells in PCOS patients also accelerates anovulation ( 21 ). Based on these findings, necroptosis may be a helpful diagnostic tool and therapeutic target for PCOS.…”

Section: Introductionmentioning

confidence: 99%

A novel model based on necroptosis to assess progression for polycystic ovary syndrome and identification of potential therapeutic drugs

Wang,

An,

Huang

et al. 2023

Front. Endocrinol.

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BackgroundPolycystic ovary syndrome (PCOS), a common endocrine and reproductive disorder, lacks precise diagnostic strategies. Necroptosis was found to be crucial in reproductive and endocrine disorders, but its function in PCOS remains unclear. We aimed to identify differentially diagnostic genes for necroptosis (NDDGs), construct a diagnostic model to assess the progression of PCOS and explore the potential therapeutic drugs.MethodsGene expression datasets were combined with weighted gene co-expression network analysis (WGCNA) and necroptosis gene sets to screen the differentially expressed genes for PCOS. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a necroptosis-related gene signatures. Independent risk analyses were performed using nomograms. Pathway enrichment of NDDGs was conducted with the GeneMANIA database and gene set enrichment analysis (GSEA). Immune microenvironment analysis was estimated based on ssGSEA algorithm analysis. The Comparative Toxicogenomics Database (CTD) was used to explore potential therapeutic drugs for NDDGs. The expression of NDDGs was validated in GSE84958, mouse model and clinical samples.ResultsFour necroptosis-related signature genes, IL33, TNFSF10, BCL2 and PYGM, were identified to define necroptosis for PCOS. The areas under curve (AUC) of receiver operating characteristic curve (ROC) for training set and validation in diagnostic risk model were 0.940 and 0.788, respectively. Enrichment analysis showed that NDDGs were enriched in immune-related signaling pathways such as B cells, T cells, and natural killer cells. Immune microenvironment analysis revealed that NDDGs were significantly correlated with 13 markedly different immune cells. A nomogram was constructed based on features that would benefit patients clinically. Several compounds, such as resveratrol, tretinoin, quercetin, curcumin, etc., were mined as therapeutic drugs for PCOS. The expression of the NDDGs in the validated set, animal model and clinical samples was consistent with the results of the training sets.ConclusionIn this study, 4 NDDGs were identified to be highly effective in assessing the progression and prognosis of PCOS and exploring potential targets for PCOS treatment.

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“…Studies have stated that hormone abnormalities in PCOS can overstimulate the immune system, and concurrently, inflammatory cell infiltration aggravates ovarian dysfunction and metabolic disorders [ 35 , 36 ]. High infiltrating abundances of macrophages [ 37 ], neutrophils, activated dendritic cells [ 38 ], and eosinophils [ 39 , 40 ] were observed in PCOS. Since chronic low-level inflammation plays a critical role in PCOS [ 41 ], we investigated and compared the immune infiltration and cytokine levels in different groups.…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenosine regulator-mediated methylation modification patterns and immune infiltration characterization in Polycystic Ovary Syndrome (PCOS)

2023

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Background Polycystic ovary syndrome (PCOS) is a multisystem-related disease whose pathophysiology is still unclear. Several regulators of N6-methyladenosine (m6A) modification were confirmed to play a regulatory role in PCOS. Nonetheless, the roles of m6A regulators in PCOS are not fully demonstrated. Materials and methods Four mRNA expression profiling microarrays were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed m6A regulators between PCOS and normal patients were identified by R software. A random forest modal and nomogram were developed to assess the relationship between m6A regulators and the occurrence risk of PCOS. A consensus clustering method was utilized to distinctly divide PCOS patients into two m6A subtypes (m6A cluster A/B). The patterns of differential expression and immune infiltration were explored between the two m6A clusters. Results In this study, 22 significant m6A regulators were identified between healthy controls and PCOS patients. The random forest model determined three optimal m6A regulators which are related to the occurrence risk of PCOS, including YTHDF1, RBM15 and METTL14. A nomogram was established based on these genes, and its predictive reliability was validated by decision curve analysis. The consensus clustering algorithm distinctly divided PCOS cases into two m6A subtypes. The ssGSEA algorithm found that the immune infiltration was markedly enriched in m6A cluster B than in cluster A. The m6A-pattern related differentially expressed genes (DEGs) of the two m6A subtypes were demonstrated by differential expression analysis. We found that they were enriched in immune-related genes and various infection pathways. Based on the m6A-pattern related DEGs, the PCOS patients were classified into two m6A-pattern related genomic subtypes (gene clusters A and B). Conclusions The present study provided evidence concerning the different modification patterns of m6A regulators in PCOS compared with normal patients. This study will help clarify the overall impact of m6A modification patterns and related immune infiltration on PCOS.

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Bioinformatics searching of diagnostic markers and immune infiltration in polycystic ovary syndrome

Cited by 8 publications

References 70 publications

Homeobox regulator Wilms Tumour 1 is displaced by androgen receptor at cis-regulatory elements in the endometrium of PCOS patients

Homeobox regulator Wilms Tumour 1 is displaced by androgen receptor at cis-regulatory elements in the endometrium of PCOS patients

A novel model based on necroptosis to assess progression for polycystic ovary syndrome and identification of potential therapeutic drugs

N6-methyladenosine regulator-mediated methylation modification patterns and immune infiltration characterization in Polycystic Ovary Syndrome (PCOS)

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