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pmid:36675186

Cross-Talk between N6-Methyladenosine and Their Related RNAs Defined a Signature and Confirmed m6A Regulators for Diagnosis of Endometriosis.

Xiaotong Wang · Xibo Zhao · Jing Wang · Han Wu · Yan Cheng · Qiuyan Guo · Tian Liang · Guangmei Zhang

International journal of molecular sciences · 2023 doi:10.3390/ijms24021665

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title
Cross-Talk between N6-Methyladenosine and Their Related RNAs Defined a Signature and Confirmed m6A Regulators for Diagnosis of Endometriosis.
doi
10.3390/ijms24021665
pmid
36675186
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Xiaotong Wang
[1]
Xibo Zhao
[2]
Jing Wang
[3]
Han Wu
[4]
Yan Cheng
[5]
Qiuyan Guo
[6]
Tian Liang
[7]
Guangmei Zhang
journal
International journal of molecular sciences
year
2023
abstract
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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These m6As were integrated based on LASSO binomial analysis with 10-fold cross-validation (Figure 6B).
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sections[9] "2.7. Construction and Validation of an m6A-Related Diagnostic Signature" paragraph 2
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These m6As were integrated based on LASSO binomial analysis with 10-fold cross-validation (Figure 6B).
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The model was further validated using two independent cohorts, and the AUC remained at 0.875 and 0.984, representing an excellent generalization (Figure 6F).
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sections[9] "2.7. Construction and Validation of an m6A-Related Diagnostic Signature" paragraph 2
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The model was further validated using two independent cohorts, and the AUC remained at 0.875 and 0.984, representing an excellent generalization (Figure 6F).
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The model was further validated using two independent cohorts, and the AUC remained at 0.875 and 0.984, representing an excellent generalization (Figure 6F).
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application/vnd.ncbi.geo-series+json
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE86534
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null
bytes
null
access
open
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resolved
reader
null
reader_status
reader_required
identifier
GSE86534
version
null
note
We are ready to provide details regarding this if published.
structure object · 15 fields
repository
GEO
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GEO accession URL
access_statement_verbatim
We are ready to provide details regarding this if published.
access_statement_kind
data_availability_statement
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[0]
GSM2305279
[1]
GSM2305280
[2]
GSM2305281
[3]
GSM2305282
[4]
GSM2305283
[5]
GSM2305284
[6]
GSM2305285
[7]
GSM2305286
[8]
GSM2305287
[9]
GSM2305288
[10]
GSM2305289
[11]
GSM2305290
sample_count
12
group_sizes
null
group_sizes_basis
null
platform
20115
taxon
Homo sapiens
title
Genome-wide long non-coding RNAs and mRNAs analysis of the tissues related to ovarian endometriosis
resolution_checked_at
2026-11-01T18:46:34Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 6 items
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[2]
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[3]
asset:data:geo:GSE141549 licence not read
[4]
asset:data:geo:GSE86534 not downloaded
[5]
asset:data:geo:GSE86534 licence not read
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state
partial
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method-1
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group_comparison
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wilcoxon
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missing_operations array · 1 item
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group_comparison_wilcoxon
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parameters object · 0 fields
data_shapes array · 1 item
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two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
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high
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Wilcoxon
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method-2
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group_comparison
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anova
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Group comparison
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group_summary
[1]
welch_t
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two_or_more_groups_continuous
evidence object · 3 fields
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0.8
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ANOVA
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method-3
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differential_expression
specific
limma_voom
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Differential expression analysis
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[1]
differential_expression_fit
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fdr_bh
missing_operations array · 0 items
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count_matrix_with_condition
evidence object · 3 fields
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0.7
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medium
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limma
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method-4
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regression_modelling
specific
logistic
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Regression modelling
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glm_logit_fit
missing_operations array · 0 items
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data_shapes array · 1 item
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evidence object · 3 fields
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method-5
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clustering
specific
kmeans
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Clustering
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[0]
kmeans_fit
missing_operations array · 0 items
parameters object · 0 fields
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[0]
feature_matrix
evidence object · 3 fields
score
0.7
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method-6
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null
specific
null
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LASSO binomial analysis with 10-fold cross-validation
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missing_operations array · 0 items
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data_shapes array · 0 items
evidence object · 3 fields
score
1
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verbatim
quote
These m6As were integrated based on LASSO binomial analysis with 10-fold cross-validation (Figure 6B).
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gaps array · 2 items
[0]
method.reader_named_unmapped
[1]
method.group_comparison_wilcoxon
capability object · 3 fields
state
complete
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capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
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survival_analysis
[3]
statistical_regression
[4]
pca
[5]
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[6]
network_analysis
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differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
state
complete
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R1
blocked_on
nothing:replicable_now
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false
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group_comparison_wilcoxon
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The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
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true
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[0]
GSE141549
[1]
GSE86534
[2]
GSE105764
resolved_accessions array · 3 items
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GSE141549
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GSE86534
[2]
GSE105764
statements array · 1 item
[0]
We are ready to provide details regarding this if published.
basis
The paper names GSE141549, GSE86534, GSE105764 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
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assets array · 2 items
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source:pmid:36675186
[1]
data:geo:GSE105764
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group_comparison_wilcoxon
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null
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data:geo:GSE105764
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review object · 5 fields
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partial
machine_critique object · 5 fields
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extraction_review
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MiniMax-M3.1-Flash
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minimax
provider_family
minimax
read_at
2026-11-01T18:23:54Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
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5
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11259
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1434
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128
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[0] object · 4 fields
id
extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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review.human_critique
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null
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execution.not_run
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pmid:36675186
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paper
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pmid:36675186
[1] object · 3 fields
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source:pmid:36675186
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manuscript
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PMID 36675186 full text
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data:geo:GSE105764
type
dataset
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GEO GSE105764
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[0] object · 4 fields
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activity-reading-sci-2026-11-01
type
classification
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pmid:36675186
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paper
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pmid:36675186
[1] object · 3 fields
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source:pmid:36675186
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manuscript
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PMID 36675186 full text
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GEO GSE105764
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agent:corpus-assay-engine
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extraction
used array · 1 item
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agent:minimax-reader
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activity-resolve-GSE105764
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accession_resolution
used array · 1 item
[0]
data:geo:GSE105764
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agent:corpus-assay-engine
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agent:corpus-assay-engine
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agent:minimax-reader
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343fb30756ba6ec3
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lineage object · 4 fields
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least in the ectopic group (Figure 8A). The RT-qPCR experiment revealed the significant differen
[1]
ast in the ectopic group (Figure 8A). The RT-qPCR experiment revealed the significant differen
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assay:1
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36675186", "kind": "science-record", "revision": 3, "content_hash": "sha256:9d579c33d77f2766e69299752716dbe234f22f7db6f476a7a8777d57755724c0", "created_at": "2026-11-01T19:01:13Z", "updated_at": "2026-11-01T22:08:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Cross-Talk between N6-Methyladenosine and Their Related RNAs Defined a Signature and Confirmed m6A Regulators for Diagnosis of Endometriosis.", "doi": "10.3390/ijms24021665", "pmid": "36675186", "authors": ["Xiaotong Wang", "Xibo Zhao", "Jing Wang", "Han Wu", "Yan Cheng", "Qiuyan Guo", "Tian Liang", "Guangmei Zhang"], "journal": "International journal of molecular sciences", "year": 2023, "abstract": "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.", "claims": [{"id": "claim-method", "statement": "These m6As were integrated based on LASSO binomial analysis with 10-fold cross-validation (Figure 6B).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36675186", "locator": "sections[9] \"2.7. Construction and Validation of an m6A-Related Diagnostic Signature\" paragraph 2", "quote": "These m6As were integrated based on LASSO binomial analysis with 10-fold cross-validation (Figure 6B)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We are ready to provide details regarding this if published.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36675186", "locator": "sections[33] \"notes\" paragraph 1", "quote": "We are ready to provide details regarding this if published."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The model was further validated using two independent cohorts, and the AUC remained at 0.875 and 0.984, representing an excellent generalization (Figure 6F).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36675186", "locator": "sections[9] \"2.7. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE105764"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE105764"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36675186", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": 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