Identifying shared molecular landscape between uterine fibroids and recurrent implantation failure: An integrated bioinformatics study

Abstract

Introduction: Infertility is a significant global issue. Infertile couples may attempt assisted reproductive techniques (ARTs), yet these are sometimes ineffective due to factors including recurrent implantation failure (RIF) which can be affected by conditions like uterine fibroids (UFs). Methods: Two gene expression (GSE64763 and GSE92324) and one methylation dataset (GSE120854) were obtained. The differentially expressed and methylated genes related to UFs and RIF were identified based on the following criteria: |log2 fold change| > 1, |delta beta| > 0.15, and adjusted p-values <0.05. Using weighted gene co-expression network analysis (WGCNA), and based on the criteria of |gene significance (GS)|≥0.50 and |module membership (MM)|≥0.80, key genes were identified in those modules with |r|>0.7 and adjusted p-values <0.01. Finally, the shared genes between differentially expressed genes (DEGs), differentially methylated genes (DMGs), and key genes from WGCNA were extracted. Results: 904 DEGs for RIF and 310 non-repetitive differentially expressed and methylated genes for UFs were identified. In WGCNA using the top 5000 highly variable genes and a degree of independence of 0.85 the co-expression network was established and module trait assessment was explored. Among the four modules linked to UFs, 145 key genes were identified, whereas for RIF, three modules yielded 1350 key genes. Following the intersection of UFs-DEGs (489), UFs-DMGs (10,474), RIF-DEGs (904), UFs key genes from WGCNA (145), and RIF key genes from WGCNA (1,350), three final genes were identified: EDNRB, BIRC3, and TRPC6. Research highlights the therapeutic potential of these genes, with EDNRB showing promise in targeting prostate cancer, and TRPC3 contributing to wound healing. However, direct evidence linking these genes to therapeutic interventions for RIF or UFs remains to be established. Conclusion: In conclusion, the objective of this study was to analyze the data of UFs and RIF in order to identify shared genes and pathways between these conditions. Three key genes have been identified in this study. Functional analysis suggested that targeting EDNRB, known for its role in cancer therapies, could be explored to modulate cellular processes in UFs and RIF. Similarly, BIRC3, which is involved in the regulation of apoptosis, may offer therapeutic potential for reducing abnormal tissue growth and enhancing implantation success. TRPC6, with its role in wound healing and cellular repair, presents opportunities for therapeutic intervention aimed at restoring endometrial receptivity. Targeting these genes could lead to treatments addressing the root causes of UFs and RIF, benefiting affected patients. Further studies are needed to validate these findings and explore their clinical potential. © 2025