Meta-analysis identifies candidate key genes in endometrium as predictive biomarkers for clinical pregnancy in IVF

Abstract

Genetic factors in endometrium are likely to be involved in the embryo implantation failure (IF), one of the major limiting factors in the success of in vitro fertilization (IVF). In this study, we aimed to identify critical genes from the transcriptional profile for the establishment of the endometrial receptivity which supporting the normal pregnancy. Three GEO datasets, including 12 samples of IF and 12 samples of controls, were used for the meta-analysis. We identified 182 different expression genes (DEGs) by comparing IF with controls and present here the successful clustering according to sample type, not by the origin. The gene ontology (GO) enriched analysis demonstrated the significant downregulation in activation and regulation of inflammatory and immune response in IF patients. Furthermore, network analysis of down-regulated genes identified the significant hub genes containing GADD45A (growth arrest and DNA damage inducible alpha, Degree = 77), GZMB (granzyme B, Degree = 38) and NLRP2 (NLR family pyrin domain containing 2, Degree = 37). The lower expression of NLRP2, related to inflammatory responses with the most degree in the network, was validatied by other GEO data. Besides, it was confirmed that the NLRP2 could act as a predictor for pregnancy after IVF (AUC = 87.93%; sensitivity, 60.00%; specificity, 91.30% ). Our meta-analysis will help us to better understand the molecular regulation of endometrial receptivity, and guiding further line of treatment for IF during IVF.