Common and specific gene signatures among three different endometriosis subtypes

Area of Science:

• Molecular biology
• Genomics
• Bioinformatics

Background:

• Endometriosis (EMs) comprises distinct subtypes: ovarian (OE), peritoneal (PE), and deep infiltrating (DIE).
• Understanding the molecular underpinnings of these subtypes is crucial for targeted therapies.

Purpose of the Study:

• To identify common and specific molecular mechanisms differentiating OE, PE, and DIE.
• To elucidate shared pathogenic pathways and subtype-specific molecular signatures in endometriosis.

Main Methods:

• Utilized four microarray datasets (GSE7305, GSE7307, E-MTAB-694, GSE25628) comparing ectopic (EC) and eutopic (EU) endometrial tissues.
• Performed differential gene expression (DEG) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) network construction.
• Validated key findings, including five hub genes, in an independent OE RNA-sequencing dataset (GSE105764).

Main Results:

• Identified 148 common DEGs and 729 (OE), 777 (PE), 36 (DIE) specific DEGs.
• Common DEGs highlighted activated arachidonic acid (AA) metabolism, indicating inflammation as a shared pathogenic process.
• Five hub genes (AURKB, RRM2, DTL, CCNB1, CCNB2) involved in cell cycle regulation were downregulated, suggesting controlled proliferation in ectopic lesions.
• Specific DEGs revealed abnormal ovarian steroidogenesis in OE, enrichment in cancer pathways for OE and DIE, and immune/inflammatory dysregulation in PE.

Conclusions:

• Common molecular signatures across endometriosis subtypes include inflammation via AA metabolism and controlled cell proliferation.
• OE and DIE present a higher risk for malignant development, while PE is associated with peritoneal immune dysregulation.
• These findings deepen the understanding of endometriosis heterogeneity and potential therapeutic targets.