From Gene Networks to Repurposed Drugs: A Systems Biomedicine Approach to Endometriosis Management
Öz
Aim: Endometriosis is a widespread gynecological condition with no definitive cure, often managed through hormonal therapies, NSAIDs, and laparoscopy, which remains the gold standard for both diagnosis
and treatment. Its underlying pathogenesis remains unclear. The absence of effective treatment options for endometriosis underscores the urgent need for innovative approaches to alleviate patient pain and
improve quality of life. This study explores an alternative therapeutic strategy for endometriosis utilizing systems biomedicine approaches.
Materials and Methods: Gene expression data from six endometrial tissue datasets (GSE135485, GSE153740, GSE232713, GSE51981, GSE23339, and GSE25628) were retrieved from the publicly available database Gene Expression Omnibus (GEO) and analyzed via GEO2R to identify differentially expressed genes (DEGs). To assess the statistical significance, p-value ≤ 0.05, log2FC > 1, and log2FC <-1 cut-offs were applied. A three-layered biological network comprising transcription factor-gene interaction, protein– protein interactions, and microRNA-gene interactions was constructed using Cytoscape to identify keyhub genes. To assess the discriminatory capacity of the hub genes between healthy and diseased groups, principal component analysis (PCA) was conducted independently for each dataset. Key genes as the
primary contributors to group differentiation were further evaluated by survival analysis.
Results: The construction of a multi-layered network analysis revealed 25 hub molecules that were used for in silico drug repositioning, and among 50 candidate compounds, fluticasone propionate, pyrimethamine, and manumycin A emerged as promising therapies. Molecular docking analysis confirmed that candidate repurposed drugs exhibited stronger binding to their respective proteins compared with known inhibitors. Additionally, PCA analysis demonstrated good sensitivity (≥80%) and moderate specificity (≈50%) in distinguishing endometriosis patients from healthy controls. Survival analysis via KM-plotter revealed the diagnostic and prognostic power of the hub genes (CXADR, RELA, STXBP6, ANK3, and PDGFR), further supporting their therapeutic potential in endometriosis.
Conclusion: Fluticasone propionate has emerged as a promising candidate for the management of endometriosis based on systems biomedicine approaches.
Anahtar Kelimeler
systems biomedicine, drug repositioning, endometriosis, transcriptomics, fluticasone propionate, manumycin A
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