Meta-analysis of endometrial transcriptome data reveals novel molecular targets for recurrent implantation failure.

ABSTRACT

PURPOSE: Gene expression analysis of the endometrium has been shown to be a useful approach for identifying the molecular signatures and pathways involved in recurrent implantation failure (RIF). Nevertheless, individual studies have limitations in terms of study design, methodology and analysis to detect minor changes in expression levels or identify novel gene signatures associated with RIF. METHOD: To overcome this, we conducted an in silico meta-analysis of nine studies, the systematic collection and integration of gene expression data, utilizing rigorous selection criteria and statistical techniques to ensure the robustness of our findings. RESULTS: Our meta-analysis successfully unveiled a meta-signature of 49 genes closely associated with RIF. Of these genes, 38 were upregulated and 11 downregulated in RIF patients' endometrium and believed to participate in key processes like cell differentiation, communication, and adhesion. GADD45A, IGF2, and LIF, known for their roles in implantation, were identified, along with lesser-studied genes like OPRK1, PSIP1, SMCHD1, and SOD2 related to female infertility. Many of these genes are involved in MAPK and PI3K-Akt pathways, indicating their role in inflammation. We also investigated to look for key miRNAs regulating these 49 dysregulated mRNAs as potential diagnostic biomarkers. Along with this, we went to associate protein-protein interactions of 49 genes, and we could recognize one cluster consisting of 11 genes (consisted of 22 nodes and 11 edges) with the highest score (p = 0.001). Finally, we validated some of the genes by qRT-PCR in our samples. CONCLUSION: In summary, the meta-signature genes hold promise for improving RIF patient identification and facilitating the development of personalized treatment strategies, illuminating the multifaceted nature of this complex condition.