The Intersection of m6A Methylation and Immune Response in PCOS: A Bioinformatics Perspective

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder, the molecular underpinnings of which remain largely undefined. The most common methylation modification of RNA, N⁶-methyladenosine (m6A), plays an important role in various reproductive and endocrine disorders. This study investigates key m6A genes in PCOS and their association with immune cell infiltration using advanced bioinformatics methods.

We utilized gene expression data and clinical information from the Gene Expression Omnibus database data sets GSE137684, GSE80432, and GSE114419. The expression of m6A-related genes was analyzed across all samples. Using the GSVA and CIBERSORT packages in R, we developed a diagnostic model based on the m6A gene-protein interaction network, conducted enrichment analysis of hub genes, and assessed the correlation between these genes and immune cell infiltration.

Analysis of data sets GSE137684 and GSE804322 identified variable expression patterns among three categories of m6A genes. A diagnostic model centered on m6A gene expression was established, highlighting five genes-WTAP, METTL14, ZC3H13, PCIF1, and RBM15-with significant effect coefficients. Unsupervised clustering of hub genes indicated that METTL14, HNRNPA2B1, YTHDF3, YTHDF2, YTHDC1, and YTHDC2 are potential discriminators in PCOS. The analysis of immune infiltration revealed a correlation between m6A regulators and immune cell levels, with METTL3 showing the most significant regulatory impact.

N⁶-methyladenosine RNA methylation regulators are intricately linked with the development of PCOS and may influence immune cell infiltration in affected individuals. This study enhances our understanding of the molecular interactions in PCOS and suggests potential biomarkers for diagnosis and targets for therapeutic intervention.