Dataset Information

Exploring diagnostic m6A regulators in endometriosis.

ABSTRACT: Endometriosis is an estrogen-dependent inflammatory disorder, usually causing infertility, pelvic pain, and ovarian masses. This study intended to investigate the implication of N6-methyladenosine (m6A) regulators in endometriosis. We acquired 34 normal, 127 eutopic, and 46 ectopic, samples of endometrium from the Gene Expression Omnibus (GSE7305, GSE7307, GSE51981) database and the Array-express (E-MTAB-694) database. These samples were then used to profile the expression of 20 m6A regulators in endometriosis. The results indicated that most dysregulated (19/20) m6A regulators were significantly downregulated in eutopic vs. normal endometrium and also significantly downregulated in ectopic vs. eutopic endometrium. Several dysregulated m6A regulators were common to both contrast matrices: METTL3, YTHDF2, YTHDF3, HNRNPA2B1, HNRNPC, and FTO. Both HNRNPA2B1 and HNRNPC were associated with the severity of endometriosis in eutopic samples, and also exhibited diagnostic potential for endometriosis. HNRNPA2B1 and HNRNPC may influence immune pathways and the infiltration of immune cells in endometriosis. Abnormalities in the gene transcription factors network associated with endometriosis might affect the expression of HNRNPA2B1 and HNRNPC. In conclusion, we observed significant dysregulation of m6A regulators in endometriosis, and found that HNRNPA2B1 and HNRNPC might correlate with the immune response and serve as useful diagnostic biomarkers for endometriosis.

SUBMITTER: Jiang L

PROVIDER: S-EPMC7803542 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Exploring diagnostic m6A regulators in endometriosis.

Jiang Li L Zhang Mengmeng M Wu Jingni J Wang Sixue S Yang Xiang X Yi Mingyu M Zhang Xinyue X Fang Xiaoling X

Aging 20201124 24

Endometriosis is an estrogen-dependent inflammatory disorder, usually causing infertility, pelvic pain, and ovarian masses. This study intended to investigate the implication of N6-methyladenosine (m6A) regulators in endometriosis. We acquired 34 normal, 127 eutopic, and 46 ectopic, samples of endometrium from the Gene Expression Omnibus (GSE7305, GSE7307, GSE51981) database and the Array-express (E-MTAB-694) database. These samples were then used to profile the expression of 20 m6A regulators i ...[more]

PMID: 33232273

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Project description:An RNA modification known as N6-methyladenosine (m6A) interacts with a range of coding and non-coding RNAs. The majority of the research has focused on identifying m6A regulators that are differentially expressed in endometriosis, but it has ignored their mechanisms that are derived from the alterations of modifications among RNAs, affecting the disease progression primarily. Here, we aimed to investigate the potential roles of m6A regulators in the diagnostic potency, immune microenvironment, and clinicopathological features of endometriosis through interacting genes. A GEO cohort was incorporated into this study. Variance expression profiling was executed via the "limma" R package. Pearson analysis was performed to investigate the correlations among 767 interacting lncRNAs, 374 interacting mRNAs, and 23 m6A regulators. K-means clustering analysis, based on patterns of mRNA modifications, was applied to perform clinical feature analysis. Infiltrating immune cells and stromal cells were calculated using the Cibersort method. An m6A-related risk model was created and supported by an independent risk assay. LASSO regression analysis and Cox analyses were implemented to determine the diagnostic genes. The diagnostic targets of endometriosis were verified using PCR and the WB method. Results: A thorough investigation of the m6A modification patterns in the GEO database was carried out, based on mRNAs and lncRNAs related to these m6A regulators. Two molecular subtypes were identified using unsupervised clustering analysis, resulting in further complex infiltration levels of immune microenvironment cells in diversified endometriosis pathology types. We identified two m6A regulators, namely METTL3 and YTHDF2, as diagnostic targets of endometriosis following the usage of overlapping genes to construct a diagnostic m6A signature of endometriosis through multivariate logistic regression, and we validated it using independent GSE86534 and GSE105764 cohorts. Finally, we found that m6A alterations might be one of the important reasons for the progression of endometriosis, especially with significant downregulation of the expressions of METTL3 and YTHDF2. Finally, m6A modification patterns have significant effects on the diversity and complexity of the progression and immune microenvironment, and might be key diagnostic markers for endometriosis.

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Dataset Information

Exploring diagnostic m6A regulators in endometriosis.

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Exploring diagnostic m6A regulators in endometriosis.

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