Exploration of the core protein network under endometriosis symptomatology using a computational approach

BACKGROUND: Endometriosis is defined by implantation and invasive growth of endometrial tissue in extra-uterine locations causing heterogeneous symptoms, and a unique clinical picture for each patient. Understanding the complex biological mechanisms underlying these symptoms and the protein networks involved may be useful for early diagnosis and identification of pharmacological targets. METHODS: In the present study, we combined three approaches (i) a text-mining analysis to perform a systematic search of proteins over existing literature, (ii) a functional enrichment analysis to identify the biological pathways in which proteins are most involved, and (iii) a protein–protein interaction (PPI) network to identify which proteins modulate the most strongly the symptomatology of endometriosis. RESULTS: Two hundred seventy-eight proteins associated with endometriosis symptomatology in the scientific literature were extracted. Thirty-five proteins were selected according to degree and betweenness scores criteria. The most enriched biological pathways associated with these symptoms were (i) Interleukin-4 and Interleukin-13 signaling (p = 1.11 x 10(-16)), (ii) Signaling by Interleukins (p = 1.11 x 10(-16)), (iii) Cytokine signaling in Immune system (p = 1.11 x 10(-16)), and (iv) Interleukin-10 signaling (p = 5.66 x 10(-15)). CONCLUSION: Our study identified some key proteins with the ability to modulate endometriosis symptomatology. Our findings indicate that both pro- and anti-inflammatory biological pathways may play important roles in the symptomatology of endometriosis. This approach represents a genuine systemic method that may complement traditional experimental studies. The current data can be used to identify promising biomarkers for early diagnosis and potential therapeutic targets.