Zeng Yulu, Gan Jiayi, Cheng Jinlian, Wei Changqiang, Zhu Xiangyun, Wei Shisi, Pang Lihong
Department of Prenatal Diagnosis, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Guangxi Key Laboratory of Thalassemia Research, Nanning, Guangxi, Guangxi, China.
Sci Rep. 2025 Jan 3;15(1):715. doi: 10.1038/s41598-024-84135-3.
Early missed abortion is defined as a pregnancy of ≤ 12 weeks in which there is a cessation of life in the developing embryo or fetus, leading to its retention within the uterine cavity without being spontaneously expelled promptly. This condition is commonly observed and significantly impacts human reproductive health. This study aimed to identify key genes related to ferroptosis that could serve as novel biomarkers for early missed abortion. Findings from gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicate a correlation between iron- DEFRGS in key modules and the p53 signaling, mitophagy-animal, and protein digestion and absorption pathways. An analysis of the protein-protein interaction (PPI) network was conducted on DEFRGs, identifying five central genes (TP53, EZH2, TIMP1, SLC3A2, and GABARAPL2) using STRING and Cytohubba ROC curves. The expression of pivotal genes in both the missed-abortion and control groups was verified by RT-qPCR. CIBERSORT analysis revealed a notable increase in the infiltration levels of CD8 + T lymphocytes and M2 macrophages among individuals in the early missed abortion group. Additionally, a ceRNA network was constructed to predict interactions between mRNA, miRNA, and lncRNA of the central genes. However, the interacting miRNAs predicted for SLC3A2 in the miRanda, miRDB, and TargetScan databases were limited to hsa-miR-661 and hsa-miR-4311, with no interacting lncRNAs found in the spongeScan database. This research has identified novel genes that could be targeted for the early detection and management of missed abortions.
早期稽留流产的定义为妊娠≤12周，此时发育中的胚胎或胎儿停止发育，导致其滞留在宫腔内而未及时自然排出。这种情况较为常见，对人类生殖健康有重大影响。本研究旨在确定与铁死亡相关的关键基因，这些基因可作为早期稽留流产的新型生物标志物。基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析结果表明，关键模块中的铁相关差异表达基因（DEFRGs）与p53信号通路、线粒体自噬-动物通路以及蛋白质消化吸收通路之间存在相关性。对DEFRGs进行了蛋白质-蛋白质相互作用（PPI）网络分析，使用STRING和Cytohubba ROC曲线确定了五个核心基因（TP53、EZH2、TIMP1、SLC3A2和GABARAPL2）。通过RT-qPCR验证了稽留流产组和对照组中关键基因的表达。CIBERSORT分析显示，早期稽留流产组个体中CD8 + T淋巴细胞和M2巨噬细胞的浸润水平显著增加。此外，构建了一个竞争性内源RNA（ceRNA）网络来预测核心基因的mRNA、miRNA和lncRNA之间的相互作用。然而，在miRanda、miRDB和TargetScan数据库中预测的与SLC3A2相互作用的miRNA仅限于hsa-miR-661和hsa-miR-4311，在spongeScan数据库中未发现相互作用的lncRNA。本研究确定了可作为稽留流产早期检测和管理靶点的新基因。
