Comparative transcriptomic analysis of endometrial tissue associated with uterine fibroids and endometrial polyps

Uterine fibroids (UFs) and endometrial polyps (EPs) are common benign gynecological conditions with distinct anatomical origins. However, their molecular impact on endometrial function remains poorly understood. This study aimed to descriptively explore shared and condition‑associated transcriptomic patterns within endometrial tissue by analyzing pathological endometrial tissue (PET) and adjacent macroscopically normal endometrial tissue (NET), sampled from areas without visible lesions in uteri affected by UFs or EPs. Paired PET and NET samples were collected during hysteroscopy from women diagnosed with UFs or EPs, with RNA‑sequencing performed on samples derived from premenopausal and perimenopausal patients. RNA sequencing and differential gene expression analysis were performed using DESeq2, followed by functional enrichment via GO and Reactome databases. Only nine differentially expressed genes (DEGs) were identified when comparing NET samples associated with UFs and EPs. In contrast, comparison of PET samples between UFs and EPs revealed 398 DEGs. Furthermore, PET versus NET comparisons demonstrated a pronounced quantitative difference between conditions, with 3163 DEGs identified in EPs and only 77 DEGs in UFs. EP-associated DEGs were enriched in immune activation, epithelial remodeling, and hormonal signaling pathways, while UF-associated DEGs reflected localized changes in inflammation, oxidative stress, and extracellular matrix remodeling. A small subset of genes (FOSB, DPP4, TM4SF4, DNER, AOX1, and PAEP) was consistently dysregulated across both conditions, suggesting shared transcriptional patterns associated with altered tissue contexts. This exploratory study provides insights into transcriptomic features of endometrial tissue associated with UFs and EPs. The findings highlight both shared and context‑dependent transcriptional patterns and identify candidate genes that warrant further investigation in future, independent studies aimed at elucidating endometrial responses to benign uterine pathology.