genel tıp derg Genel Tıp Dergisi 2602-3741 Selçuk Üniversitesi 10.54005/geneltip.1812858 Medical Genetics (Excl. Cancer Genetics) Tıbbi Genetik (Kanser Genetiği hariç) Gen Ağlarından Yeniden Konumlandırılmış İlaçlara: Endometriozis Yönetiminde Sistem Biyotıbbı Yaklaşımı From Gene Networks to Repurposed Drugs: A Systems Biomedicine Approach to Endometriosis Management https://orcid.org/0009-0003-1701-3860 Taş Fadime Dilşad konya gıda ve tarım üniversitesi https://orcid.org/0000-0002-8832-8443 Aydın Büşra KONYA GIDA VE TARIM ÜNİVERSİTESİ 03 30 2026 36 2026 1 13 10 30 2025 02 03 2026 Copyright © 1990, Genel Tıp Dergisi 1990 Genel Tıp Dergisi

Amaç: Endometriozis, kesin bir tedavisi bulunmayan, yaygın görülen bir jinekolojik hastalıktır. Günümüzde genellikle hormonal tedaviler, nonsteroidal antiinflamatuvar ilaçlar (NSAID’ler) ve hem tanı hem detedavide altın standart kabul edilen laparoskopi ile yönetilmektedir. Ancak hastalığın altta yatan patogenezi hâlâ tam olarak aydınlatılamamıştır. Endometriozisin etkili tedavi seçeneklerinin sınırlı olması, hasta ağrısını hafifletmek ve yaşam kalitesini artırmak için yenilikçi yaklaşımlara duyulan acil ihtiyacı ortaya koymaktadır. Bu çalışma, sistem biyotıbbı yaklaşımlarını kullanarak endometriozis için alternatif bir terapötik strateji geliştirmeyi amaçlamaktadır.Gereç ve Yöntemler: Altı endometriyal dokuya ait veri setine (GSE135485, GSE153740, GSE232713, GSE51981, GSE23339 ve GSE25628) ait gen ekspresyon verileri, açık erişimli Gene Expression Omnibus (GEO) veritabanından alınmıştır. Veriler, farklı şekilde eksprese edilen genleri (DEG) belirlemek amacıyla GEO2R aracı kullanılarak analiz edilmiştir. İstatistiksel anlamlılık değerlendirmesinde p ≤ 0.05, log2FC >1 ve log2FC< -1 eşik değerleri uygulanmıştır. Anahtar hub genleri belirlemek amacıyla, transkripsiyon faktörü–gen etkileşimleri, protein–protein etkileşimleri ve mikroRNA–gen etkileşimlerinden oluşan üç katmanlı bir biyolojik ağ Cytoscape kullanılarak oluşturulmuştur. Biyolojik ağlardan elde edilen hub moleküllerin ekspresyon profillerini tersine çevirme amacıyla ilaç repozisyonu L1000CDS2 aracı ile gerçekleştirilmiştir. Hub moleküllerin sağlıklı ve hastalıklı grupları ayırt etme kapasitesini değerlendirmek için her bir veri seti için ayrı ayrı temel bileşen analizi (PCA) gerçekleştirilmiştir. Grup ayrımına en fazla katkı sağlayan merkezigenler ise sağkalım analizi ile daha ileri düzeyde değerlendirilmiştir.Bulgular: Ağ analiziyle elde edilen 25 gen, in silico ilaç yeniden konumlandırma çalışmaları için kullanılmış ve 50 aday bileşik arasından flutikazon propiyonat, pirimetamin ve manumisin A umut verici terapötik ajanlar olarak öne çıkmıştır. Moleküler kenetlenme analizi, bu ilaçların hedef proteinlere bilinen inhibitörlerinden daha güçlü bağlanma eğilimi gösterdiğini doğrulamıştır. Ayrıca, PCA analizi endometriozis hastalarını sağlıklı kontrollerden ayırt etmede yüksek duyarlılık (≥80%) ve orta düzeyde özgüllük (≈50%) sergilemiştir. KM-plotter aracılığıyla yapılan sağkalım analizi, merkez genlerin (CXADR, RELA, STXBP6, ANK3 ve PDGFR) tanısal ve prognostik potansiyelini ortaya koyarak, endometriozisteki terapötik önemlerini desteklemiştir.Sonuç: Sistem biyotıbbı yaklaşımlarına dayalı olarak, flutikazon propiyonat endometriozisin tedavisinde umut verici bir aday ilaç olarak öne çıkmıştır.

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 diagnosisand 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 andimprove 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 theprimary 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.

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