Lin Jia-Zhe, Lin Nuan
Neurosurgical Department, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Obstetrics and Gynecology Department, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Front Immunol. 2022 Jun 3;13:902268. doi: 10.3389/fimmu.2022.902268. eCollection 2022.
Recurrent implantation failure (RIF) represents a new challenge in the field of assisted reproductive technology (ART). Considering the known effects of immune cell regulation on embryo implantation process, as well as our gene set variation analysis (GSVA) results that suggested the association between RIF and pathways of oxidative stress and immune responses, we hypothesized that oxidative stress- related genes (OSGs) associated with aberrant immunological factor may represent novel biomarkers for unexplained RIF. We therefore screened out the immune cell coexpressed OSGs by performing CIBERSORT, LM22 matrix and Pearson correlation, followed by constructing an OSG signature by least absolute shrinkage and selection operator (LASSO) regression. Three OSGs (AXL, SLC7A11 and UBQLN1) were then identified to establish a RIF risk signature, which showed high ability to discriminating RIF from fertile control. A nomogram was established, with a free online calculator for easier clinical application. Finally, Chilibot, protein-protein interaction analysis and BioGPS were sequentially applied for the investigation of functional relationships of these three genes with RIF and other OSGs, as well as their expression abundance across different human tissues. In conclusion, we identified an OSG signature that are relevant novel markers for the occurrence of unexplained RIF.
反复种植失败(RIF)是辅助生殖技术(ART)领域面临的一项新挑战。鉴于免疫细胞调节对胚胎着床过程的已知影响,以及我们的基因集变异分析(GSVA)结果表明RIF与氧化应激和免疫反应途径之间存在关联,我们推测与异常免疫因子相关的氧化应激相关基因(OSGs)可能是不明原因RIF的新型生物标志物。因此,我们通过进行CIBERSORT、LM22矩阵和Pearson相关性分析筛选出免疫细胞共表达的OSGs,随后通过最小绝对收缩和选择算子(LASSO)回归构建OSG特征。然后鉴定出三个OSGs(AXL、SLC7A11和UBQLN1)以建立RIF风险特征,该特征显示出将RIF与正常生育对照组区分开来的高能力。建立了一个列线图,并提供了一个免费的在线计算器以便于临床应用。最后,依次应用Chilibot、蛋白质-蛋白质相互作用分析和BioGPS来研究这三个基因与RIF和其他OSGs的功能关系,以及它们在不同人体组织中的表达丰度。总之,我们鉴定出了一个与不明原因RIF发生相关的OSG特征,这些是相关的新型标志物。