Exploration of ferroptosis-related biomarkers with prognostic capability in RIF based on WGCNA.

IF 3.2 3区 医学 Q2 GENETICS & HEREDITY Journal of Assisted Reproduction and Genetics Pub Date : 2024-12-23 DOI:10.1007/s10815-024-03370-9
Tingting Zhou, Qian Zhang, Wenhao Yu, Yuqian Cui, Junhao Yan, Tianxiang Ni, Xiaohua Fu, Junwei Li
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Abstract

Purpose: To explore the association of ferroptosis with repeated implantation failure (RIF) and prognostic capability of ferroptosis-related genes.

Methods: Data in GSE106602 from the GEO database were used for gene co-expression network construction to confirm ferroptosis-related genes compared to gene sets that were downloaded from FerrDB. Then these genes were analyzed for functional enrichment and validated using endometrium samples from our center. ImplantScore and ROC curve were constructed for prognostic correlation analysis.

Results: We observed that ferroptosis probably participated in RIF according to bioinformatics analysis on a gene set which exhibited a strong association with RIF from WGCNA. Fifty-four ferroptosis-related genes in the gene set were subsequently verified, and the PPI network was established for underlying interactions among them. There were 23 hub genes with differential expression in RIF and six of them (PML, LCN2, PRKAA1, BACH1, SLC7A11, and CAMKK2) showed significant correlation with implantation outcomes using samples collected from our center. Therefore, we combined the six genes and constructed an ImplantScore whose AUC reached 0.891, higher than the AUC of each single gene, respectively. ImplantScore of six genes with down-regulated expression in the group with failed implantation were much lower than that with successful outcome.

Conclusion: Our results demonstrated the potential prognostic functions of ferroptosis-related biomarkers in RIF, which will provide novel perspectives for further research and clinical applications.

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基于WGCNA的铁中毒相关生物标志物与RIF预后能力的探索。
目的:探讨铁下垂与反复着床失败(RIF)的关系及铁下垂相关基因对预后的影响。方法:利用GEO数据库GSE106602中的数据进行基因共表达网络构建,与从FerrDB下载的基因集进行比对,确认铁衰相关基因。然后对这些基因进行功能富集分析,并使用我们中心的子宫内膜样本进行验证。构建ImplantScore和ROC曲线进行预后相关性分析。结果:通过对来自WGCNA的一组与RIF密切相关的基因进行生物信息学分析,我们发现铁下沉可能参与了RIF。随后,我们验证了基因集中54个衰铁相关基因,并建立了它们之间潜在相互作用的PPI网络。在RIF中有23个中心差异表达基因,其中PML、LCN2、PRKAA1、BACH1、SLC7A11、CAMKK2 6个中心差异表达基因与植入结果有显著相关性。因此,我们将6个基因组合在一起,构建了一个ImplantScore,其AUC分别高于单个基因的AUC,达到0.891。着床失败组6个表达下调基因的ImplantScore明显低于着床成功组。结论:我们的研究结果证明了铁死相关生物标志物在RIF中的潜在预后功能,为进一步的研究和临床应用提供了新的视角。
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来源期刊
CiteScore
5.70
自引率
9.70%
发文量
286
审稿时长
1 months
期刊介绍: The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species. The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.
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