摘要
目的 应用加权基因共表达网络分析(WGCNA)探讨反复种植失败(RIF)胚胎种植窗口期关键生物学标志物以及子宫内膜局部免疫细胞浸润情况。方法 从GEO数据库中下载基因芯片数据,以logFC≥1,P<0.05为筛选条件;以GSE103465和GSE111974作为模型组,获取RIF和正常妊娠志愿者差异表达基因(DEGs),使用GO和KEGG对DEGs进行功能富集分析。使用WGCNA和LASSO回归筛选RIF关键生物学标志物,并使用GSE26787、GSE71835和GSE92324作为验证组进行验证。基于ssGSEA分析RIF浸润免疫细胞相对丰富度以及与关键生物学标志物相关性。结果 相对于正常妊娠者,RIF患者共筛选出178个DEGs,其中高表达115个,低表达63个。WGCNA和LASSO回归证实模型组GJA1(AUC=0.875)和PHF8(AUC=0.903)是RIF密切相关的诊断性标志物,在验证组(GJA1:AUC=0.777;PHF8:AUC=0.885)同样发现佐证了该结果。而且模型组和验证组均发现RIF患者GJA1呈低表达,PHF8呈高表达,与浸润免疫细胞存在明显的相关性。RIF和正常妊娠志愿者WOI子宫内膜样本之间免疫细胞浸润存在一定的差异。结论 GJA1和PHF8能够用于RIF患者的诊断与识别,与子宫内膜浸润免疫细胞密切相关。
Objective The aim of this study was to identify the potential diagnostic biomarkers and immune cell infiltration of repeated implantation failure(RIF)in window of implantation based on Weighted correlation network analysis(WGCNA).Methods An differentially expressed genes(DEGs)analysis of publicly available microarray data was used in this study to screen differences in gene expression between RIF and healthy fertile women using logFC≥1 and P<0.05.GO and KEGG analysis were used to identify biological processes enriched in DEGs.As a result of WGCNA and LASSO algorithm screen in DEGs,potential diagnostic biomarkers were identified and then verified.In order to investigate infiltrating immune cells of RIF and the correlation between diagnostic biomarkers and infiltrating immune cells,ssGSEA were performed.Results Our findings revealed 115 genes upregulated and 63 genes downregulated in RIF,respectively.Based on WGCNA and LASSO regression,biomarkers closely associated with RIF were GJA1(AUC=0.875)and PHF8(AUC=0.903)in model group.Using the validation group,we verified this finding(GJA1:AUC=0.777;PHF8:AUC=0.885).Similar reductions in GJA1 and elevation in PHF8 were found in both groups of RIF.And a significant correlation was observed among biomarkers with infiltrating immune cells.There were some differences in immune cell infiltration between RIF and healthy fertile women in WOI.Conclusion GJA1 and PHF8 could be used in the diagnosis and identification of RIF patients,which were closely related to the infiltration of immune cells in endometrium.
作者
覃韦丽
王嘉伟
黄汉记
覃爱平
QIN Weili;WANG Jiawei;HUANG Hanji;QIN Aiping(Center of Reproductive Medicine,the First Affiliated Hospital of Guangxi Medical University,Nanning City,Guangxi Zhuang Autonomous Region,530021,China;College of Life Sciences,Guangxi Medical University,Nanning City,Guangxi Zhuang Autonomous Region,530021,China)
出处
《蛇志》
2023年第2期177-184,共8页
Journal of Snake
基金
国家自然科学基金(项目名称:Talin1调控细胞粘附在胚胎着床中的作用及其机制研究,项目编号:81960280)。
关键词
反复种植失败
加权基因共表达网络分析
差异表达基因
种植窗
子宫内膜容受性
Repeated implantation failure
Weighted correlation network analysis
Differentially expressed genes
Window of implantation
Endometrial receptivity
