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Updated: Aug 3, 2025
Evaluation of Hepatic Glucose Production in a Polycystic Ovary Syndrome Mouse Model
Published on: March 5, 2022
N6-methyladenosine regulator-mediated methylation modification patterns and immune infiltration characterization in
Sihan Zhou1,2, Rui Hua3, Song Quan4
1Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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.
Insights
Polycystic ovary syndrome (PCOS) involves complex N6-methyladenosine (m6A) modifications. This study identifies key m6A regulators and distinct molecular subtypes in PCOS, revealing links to immune infiltration and infection pathways.
Area of Science:
- Endocrinology
- Molecular Biology
- Genomics
Background:
- Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with unclear pathophysiology.
- N6-methyladenosine (m6A) modification regulators are implicated in PCOS, but their roles require further elucidation.
Purpose of the Study:
- To identify differentially expressed m6A regulators in PCOS.
- To develop a predictive model for PCOS risk based on m6A regulators.
- To classify PCOS patients into distinct molecular subtypes based on m6A patterns and explore associated immune infiltration.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) datasets for mRNA expression profiling.
- Applied R software to identify differentially expressed m6A regulators.
- Developed random forest and nomogram models for risk assessment and consensus clustering for subtype classification.
Main Results:
- Identified 22 significant m6A regulators between PCOS and normal patients.
- Three key regulators (YTHDF1, RBM15, METTL14) were identified for PCOS risk prediction.
- Distinct m6A subtypes (A and B) were classified, with subtype B showing enriched immune infiltration and pathways related to infection.
Conclusions:
- Demonstrated differential m6A modification patterns in PCOS compared to normal individuals.
- Highlighted the association between m6A regulators, immune infiltration, and distinct molecular subtypes in PCOS.
- Provided insights into the impact of m6A modification patterns on PCOS pathogenesis.
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