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代谢相关蛋白作为预测多囊卵巢综合征预后的生物标志物。

Metabolism-related proteins as biomarkers for predicting prognosis in polycystic ovary syndrome.

作者信息

Ding Nan, Wang Ruifang, Wang Peili, Wang Fang

机构信息

The addresses of the institutions: Reproductive Medicine Center, Lanzhou University Second Hospital, No.82, Cuiying Road, Chengguan District, Lanzhou City, Gansu Province, China.

出版信息

Proteome Sci. 2024 Dec 19;22(1):14. doi: 10.1186/s12953-024-00238-9.

Abstract

OBJECTIVE

The study aimed to explore the role of metabolism-related proteins and their correlation with clinical data in predicting the prognosis of polycystic ovary syndrome (PCOS).

METHODS

This research involves a secondary analysis of proteomic data derived from endometrial samples collected from our study group, which includes 33 PCOS patients and 7 control subjects. A comprehensive identification and analysis of 4425 proteins were conducted to screened differentially expressed proteins (DEPs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were subsequently performed on the DEPs. To identify independent prognostic metabolism-related proteins, univariate Cox regression and LASSO regression were applied. The expression levels of these proteins were then used to develop a prognostic model, with their predictive accuracy evaluated through receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and calibration curves. Furthermore, we also investigate the correlation between clinical data and prognostic proteins.

RESULTS

The study identified 285 DEPs between the PCOS and control groups. GO enrichment analysis revealed significant involvement in metabolic processes, while KEGG pathway analysis highlighted pathways such as glycolysis/gluconeogenesis and glucagon signaling. Ten key metabolism-related proteins (ACSL5, ANPEP, CYB5R3, ENOPH1, GLS, GLUD1, LDHB, PLCD1, PYCR2, and PYCR3) were identified as significant predictors of PCOS prognosis. Patients were separated into high and low-risk groups according to the risk score. The ROC curves for predicting outcomes at 6, 28, and 37 weeks demonstrated excellent predictive performance, with AUC values of 0.98, 1.0, and 1.0, respectively. The nomogram constructed from these proteins provided a reliable tool for predicting pregnancy outcomes. DCA indicated a net benefit of the model across various risk thresholds, and the calibration curve confirmed the model's accuracy. Additionally, we also found BMI exhibited a significant negative correlation with the expression of GLS (r =-0.44, p = 0.01) and CHO showed a significant positive correlation with the expression of LDHB (r = 0.35, p = 0.04).

CONCLUSION

The identified metabolism-related proteins provide valuable insights into the prognosis of PCOS. The protein based prognostic model offers a robust and reliable tool for risk stratification and personalized management of PCOS patients.

摘要

目的

本研究旨在探讨代谢相关蛋白在预测多囊卵巢综合征(PCOS)预后中的作用及其与临床数据的相关性。

方法

本研究对来自研究组收集的子宫内膜样本的蛋白质组学数据进行二次分析,研究组包括33例PCOS患者和7例对照受试者。对4425种蛋白质进行全面鉴定和分析,以筛选差异表达蛋白(DEP)。随后对DEP进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。为了鉴定独立的预后代谢相关蛋白,应用单变量Cox回归和LASSO回归。然后利用这些蛋白的表达水平建立预后模型,并通过受试者工作特征(ROC)曲线、决策曲线分析(DCA)和校准曲线评估其预测准确性。此外,我们还研究了临床数据与预后蛋白之间的相关性。

结果

该研究确定了PCOS组和对照组之间的285种DEP。GO富集分析显示其显著参与代谢过程,而KEGG通路分析突出了糖酵解/糖异生和胰高血糖素信号等通路。十种关键的代谢相关蛋白(ACSL5、ANPEP、CYB5R3、ENOPH1、GLS、GLUD1、LDHB、PLCD1、PYCR2和PYCR3)被确定为PCOS预后的重要预测因子。根据风险评分将患者分为高风险组和低风险组。预测6周、28周和37周结局的ROC曲线显示出优异的预测性能,AUC值分别为0.98、1.0和1.0。由这些蛋白构建的列线图为预测妊娠结局提供了可靠的工具。DCA表明该模型在各种风险阈值下均有净效益,校准曲线证实了该模型的准确性。此外,我们还发现BMI与GLS的表达呈显著负相关(r = -0.44,p = 0.01),CHO与LDHB的表达呈显著正相关(r = 0.35,p = 0.04)。

结论

所鉴定的代谢相关蛋白为PCOS的预后提供了有价值的见解。基于蛋白的预后模型为PCOS患者的风险分层和个性化管理提供了一个强大而可靠的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/548b/11660692/f8966040ce42/12953_2024_238_Fig1_HTML.jpg

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