基于焦亡相关基因构建多囊卵巢综合征诊断模型
作者:
作者单位:

1.南京医科大学附属逸夫医院;2.南京医科大学第二临床医学院;3.南京医科大学第二附属医院

基金项目:

国家自然科学基金项目(面上项目,重点项目,重大项目),江苏省卫健委医学科研项目面上项目


A diagnostic model of polycystic ovary syndrome based on the genes associated with pyroptosis
Affiliation:

1.the Affiliated Sir Run Run Hospital of Nanjing Medical University;2.the Second Affiliated Hospital of Nanjing Medical University

Fund Project:

The National Natural Science Foundation of China (General Program, Key Program, Major Research Plan)

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    摘要:

    目的: 为了探索焦亡相关的基因在多囊卵巢综合征(Polycystic ovary syndrome,PCOS)发病机制中的作用;并构建PCOS的精确预测模型。方法: 为此,从基因表达综合数据库(Gene expression Synthesis,GEO)中获取了三个微小RNA(microRNA, mRNA)表达谱,并分析了PCOS患者与正常健康女性之间焦亡相关基因(Pyroptosis-related genes,PRGs)的表达差异。本研究采用了广义线性模型(Generalized linear model,GLM)、随机森林(Random forest,RF)、支持向量机(Support vector machine,SVM)和极限梯度提升(Extreme gradient boosting,XGB),这四种机器学习算法来识别疾病特征基因。并采用实时定量聚合酶链反应(Real-time quantitative polymerase chain reaction, RT-qPCR)法检测10例PCOS患者和10例正常健康女性血浆中特征基因的表达量。结果: 建立了基于PRGs的PCOS预测模型和列线图。XGB方法在使用两个独立数据集验证模型时显示出最高的准确性,决策曲线分析进一步支持了这一结果。一致聚类显示PCOS病例中有两个不同的亚组,组2比组1表现出更高的免疫浸润。差异表达分析鉴定两个亚型之间的差异表达基因(Differentially expressed genes,DEGs) ,并对模式基因进行富集分析。临床验证,含CARD结构域的凋亡相关斑点样蛋白(PYD and CARD domain containing,PYCARD)、黑素瘤缺乏因子2(Absent in melanoma 2,AIM2)、染色质修饰蛋白4B(Chromatin modif-ying protein 4B,CHMP4B)和NOD样受体蛋白2(NOD-like receptor family pyrin domain containing 2,NLRP2)在PCOS患者组中的表达量明显高于正常对照组,具有统计学差异,验证了基于PRGs的PCOS预测模型准确性。结论: 本研究为PCOS与焦亡之间的关系提供了初步的见解,并提出了PCOS的精确预测模型。

    Abstract:

    Objective:To explore the role of genes related to pyroptosis in the pathogenesis of Polycystic ovary syndrome (PCOS) and construct an accurate prediction model for PCOS. Methods: Three micro RNA(mRNA) expression profiles were obtained from the Gene Expression Omnibus (GEO) database ,and analysis was carried out on the differential expression of pyroptosis-related genes (PRGs) between PCOS patients and normal healthy women.Four machine learning algorithms, namely the Generalized Linear Model (GLM), Random Forest (RF), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGB), were employed to identify the gene characteristics of PCOS. Real?time quantitative PCR(RT-qPCR) method was utilized to detect the expression levels of specific genes in the plasma of 10 PCOS patients and 10 normal healthy women.Results: A predictive model and a nomogram were established based on PRGs to accurately predict PCOS. Among the four machine learning algorithms,the XGB method demonstrated the highest accuracy in validating the model using two independent datasets, which was further supported by decision curve analysis. Consensus clustering revealed two distinct subgroups within PCOS cases, with Cluster2 exhibiting higher level of immune infiltration compared to Cluster1. Differential expression analysis was then conducted to identify differentially expressed genes (DEGs) between the two subtypes, followed by pathway enrichment analysis on the model genes. Clinical verification showed that the expression levels of PYD and CARD domain containing(PYCARD), Absent in melanoma 2(AIM2), Chromatin modif-ying protein 4B(CHMP4B) and NOD-like receptor family pyrin domain containing 2(NLRP2) in the plasma of PCOS patients were significantly higher than those of the healthy control group, with statistical differences. This verifies the accuracy of the PCOS prediction model based on PRGs.Conclusion: This study offers preliminary insights into the association between PCOS and pyroptosis,a precise predictive model for PCOS.

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  • 收稿日期:2024-09-29
  • 最后修改日期:2024-12-26
  • 录用日期:2025-03-07
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