Department of Reproductive Medicine, Lanzhou University Second Hospital, Lanzhou, China.
Front Endocrinol (Lausanne). 2022 Jul 14;13:871945. doi: 10.3389/fendo.2022.871945. eCollection 2022.
We aimed to study the relationship between ferroptosis proteins and reproductive outcomes of infertile patients with PCOS and construct the related prognostic model.
These endometrium samples of the study were collected from 33 women with PCOS and 7 control women with successful pregnancies at the Reproductive Center of Lanzhou University Second Hospital, September 2019 to September 2020. The 40 patients' endometrium was identified the differentially expressed proteins (DEPs) using liquid chromatography tandem mass spectrometry. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology (GO) showed that the DEPs related pathways and functions between PCOS and controls. Subsequently, univariate Cox regression analysis and Lasso regression were used to identifying independent prognostic ferroptosis proteins, which were utilized to establish a prognostic model. Then the performance of the prognostic model was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). Then clinical data and prognostic model were used to predict the reproductive outcomes of PCOS patients by constructing the nomograms. Finally, we performed the single sample gene set enrichment analysis (ssGSEA) to explore the correlation between risk scores and immune status.
A total of 5331 proteins were identified, 391 proteins were differentially expressed in the PCOS and controls. The KEGG analysis revealed that the ferroptosis pathway was significantly different between PCOS and controls. 5 ferroptosis proteins (GPX4, DPP4, G6PD, PCBP1, and PCBP2) prognostic model (FerSig) was constructed Cox regression and Lasso regression. Patients were separated into high and low-risk groups according to the FerSig. Kaplan-Meier curve showed that patients in the low-risk group had much better reproductive outcomes than those in the high-risk group. The DCA showed that the risk score was an independent predictive factor for reproductive outcomes. Compared with clinical data, ROC curve analysis indicated the FerSig proteins as a potential diagnostic and prognostic factor in PCOS patients. Functional analysis revealed that the FerSig proteins and immune microenvironment were correlated to the prognosis of PCOS.
The prognostic model focused on the FerSig proteins could predict the reproductive outcomes of PCOS patients with decreased endometrial receptivity, and provided theoretical basis for individualized treatment.
本研究旨在探讨铁死亡蛋白与多囊卵巢综合征（PCOS）不孕患者生殖结局的关系，并构建相关预后模型。
本研究收集了 2019 年 9 月至 2020 年 9 月兰州大学第二医院生殖中心 33 例 PCOS 患者和 7 例成功妊娠对照患者的子宫内膜样本。采用液相色谱串联质谱技术鉴定 40 例患者的差异表达蛋白（DEPs）。京都基因与基因组百科全书（KEGG）分析和基因本体论（GO）显示了 PCOS 与对照组之间 DEPs 相关的途径和功能。随后，采用单变量 Cox 回归分析和 Lasso 回归筛选独立的预后性铁死亡蛋白，建立预后模型。然后通过接收者操作特征曲线（ROC）和决策曲线分析（DCA）评估预后模型的性能。然后，通过构建列线图，利用临床数据和预后模型预测 PCOS 患者的生殖结局。最后，我们进行了单样本基因集富集分析（ssGSEA），以探讨风险评分与免疫状态的相关性。
共鉴定出 5331 种蛋白质，其中 391 种蛋白质在 PCOS 和对照组之间存在差异表达。KEGG 分析显示，铁死亡途径在 PCOS 和对照组之间存在显著差异。通过 Cox 回归和 Lasso 回归构建了 5 个铁死亡蛋白（GPX4、DPP4、G6PD、PCBP1 和 PCBP2）预后模型（FerSig）。根据 FerSig 将患者分为高风险组和低风险组。Kaplan-Meier 曲线显示，低风险组患者的生殖结局明显优于高风险组。DCA 显示，风险评分是生殖结局的独立预测因素。与临床数据相比，ROC 曲线分析表明 FerSig 蛋白是 PCOS 患者潜在的诊断和预后因素。功能分析表明，FerSig 蛋白与免疫微环境与 PCOS 的预后相关。
聚焦于 FerSig 蛋白的预后模型可以预测子宫内膜容受性降低的 PCOS 患者的生殖结局，为个体化治疗提供了理论依据。
