利用生物信息学分析研究复发性流产和不明原因不孕症中关键铁死亡相关基因及免疫格局。

Investigation of hub ferroptosis-related genes and the immune landscape in recurrent pregnancy loss and unexplained infertility using bioinformatics analysis.

作者信息

Nong Binbin, Liang Yuexiu, Fang Dalang, Pan Zhongmian, Li Wei, Yang Changyong, Huang Aimin, Gui Nannan, Huang Jintai, Jin Mingyang

机构信息

Department of Gynecology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

Department of Breast and Thyroid Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

出版信息

Ann Transl Med. 2023 Mar 15;11(5):209. doi: 10.21037/atm-23-97. Epub 2023 Mar 2.

DOI:10.21037/atm-23-97

PMID:37007565

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10061488/

Abstract

BACKGROUND

Recurrent pregnancy loss (RPL) and unexplained infertility (UI) are common pregnancy disorders that affect women's physical and mental health and lack effective treatment. Endometrial factors are one factor that leads to RPL. The latest research indicates that ferroptosis and immunity are closely related to the normal physiological function of the endometrium and may play a role in the pathogenesis of RPL and UI. Therefore, the present study analyzed the relationship between ferroptosis genes and immune infiltration in RPL and UI.

METHODS

We downloaded the GSE165004 dataset and analyzed differences in ferroptosis-related genes (FRGs) between RPL and UI patients and healthy controls. Hub differentially expressed ferroptosis-related genes (DE-FRGs) were screened using the LASSO algorithm, the SVM-RFE algorithm and the protein-protein interaction (PPI) network. Differences in immune infiltration between healthy endometrium and RPL and UI endometrium was analyzed, and the relationship between hub DE-FRGs and immune cell infiltration was examined.

RESULTS

We extracted 409 FRGs and identified 36 up-regulated and 32 down-regulated DE-FRGs in RPL and UI. Twenty-one genes were screened using the LASSO regression algorithm, and 17 genes were screened using the SVM-RFE algorithm. We intersected the LASSO genes, SVM-RFE genes and PPI network proteins to obtain 5 hub DE-FRGs. Gene set enrichment analysis (GSEA) functional enrichment analysis results indicated that the cytokine-cytokine receptor interaction signaling pathway was the common pathway for hub DE-FRGs. T follicular helper cells were highly infiltrated in RPL and UI, and M1 and M2 macrophages were highly infiltrated. The expression levels of and positively correlated with T follicular helper cells.

CONCLUSIONS

Ferroptosis-related genes may disrupt endometrial functions and signaling pathways and lead to the occurrence of RPL and UI.

摘要

背景

复发性流产（RPL）和不明原因不孕症（UI）是常见的妊娠疾病，会影响女性身心健康且缺乏有效治疗方法。子宫内膜因素是导致RPL的一个因素。最新研究表明，铁死亡和免疫与子宫内膜的正常生理功能密切相关，可能在RPL和UI的发病机制中起作用。因此，本研究分析了RPL和UI中铁死亡基因与免疫浸润之间的关系。

方法

我们下载了GSE165004数据集，并分析了RPL和UI患者与健康对照之间铁死亡相关基因（FRGs）的差异。使用LASSO算法、支持向量机递归特征消除（SVM-RFE）算法和蛋白质-蛋白质相互作用（PPI）网络筛选关键差异表达铁死亡相关基因（DE-FRGs）。分析了健康子宫内膜与RPL和UI子宫内膜之间免疫浸润的差异，并研究了关键DE-FRGs与免疫细胞浸润之间的关系。

结果

我们提取了409个FRGs，并在RPL和UI中鉴定出36个上调和32个下调的DE-FRGs。使用LASSO回归算法筛选出21个基因，使用SVM-RFE算法筛选出17个基因。我们将LASSO基因、SVM-RFE基因和PPI网络蛋白进行交集分析，得到5个关键DE-FRGs。基因集富集分析（GSEA）功能富集分析结果表明，细胞因子-细胞因子受体相互作用信号通路是关键DE-FRGs的共同通路。T滤泡辅助细胞在RPL和UI中高度浸润，M1和M2巨噬细胞也高度浸润。[此处原文可能缺失两个基因名称]的表达水平与T滤泡辅助细胞呈正相关。