Integrative Transcriptomic Analysis Identifies a Key Candidate Gene Bridging Inflammation and DNA Repair in...

Area of Science:

• Reproductive Biology
• Molecular Biology
• Genomics

Background:

• Endometriosis is an inflammatory disorder where endometrial tissue grows outside the uterus.
• The exact reasons why only some women develop endometriosis despite common retrograde menstruation are unclear.
• Intrinsic molecular changes in the endometrium may predispose cells to survive stress.

Purpose of the Study:

• To investigate molecular differences in the eutopic endometrium of women with endometriosis.
• To identify key genes and pathways involved in cellular adaptation to stress in endometriosis.
• To explore the role of DNA repair and immune cell infiltration in disease pathogenesis.

Main Methods:

• Analysis of eutopic endometrial transcriptomes from endometriosis patients and controls.
• Differential gene expression, pathway enrichment (GO, KEGG), and immune cell infiltration analysis (CIBERSORT).
• Identification of feature genes using protein-protein interaction networks and machine learning (MCC, RF, LASSO); evaluation of ERCC1 evolutionary conservation and structural variants.

Main Results:

• 443 differentially expressed genes were linked to inflammatory pathways (NF-κB, Toll-like receptor, cytokine signaling).
• Four key genes (ERCC1, SOX3, NGFR, FPR1) were identified, with ERCC1 showing evolutionary conservation and potential DNA repair disruption.
• Eutopic endometrium showed altered immune cell profiles (increased NK cells, decreased CD8+ T cells) correlating with feature genes.

Conclusions:

• The eutopic endometrium in endometriosis exhibits a stress-adaptive transcriptomic state driven by inflammation, immune changes, and DNA repair alterations.
• ERCC1 emerges as a potential link between inflammatory stress and impaired DNA repair, aiding lesion establishment.
• The identified gene signature reflects a DNA repair adaptation rather than a global stemness shift.