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勃起功能障碍新的脂肪酸代谢相关机制及生物标志物的鉴定与验证

Identification and validation of new fatty acid metabolism-related mechanisms and biomarkers for erectile dysfunction.

作者信息

He Yanfeng, Liu Changyi, Zheng Zhongjie, Gao Rui, Lin Haocheng, Zhou Huiliang

机构信息

Department of Urology, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.

Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.

出版信息

Sex Med. 2024 Mar 23;12(1):qfae011. doi: 10.1093/sexmed/qfae011. eCollection 2024 Feb.

Abstract

BACKGROUND

Erectile dysfunction (ED) is a common condition affecting middle-aged and elderly men.

AIM

The study sought to investigate differentially expressed fatty acid metabolism-related genes and the molecular mechanisms of ED.

METHODS

The expression profiles of GSE2457 and GSE31247 were downloaded from the Gene Expression Omnibus database and merged. Differentially expressed genes (DEGs) between ED and normal samples were obtained using the R package limma. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of DEGs were conducted using the R package clusterProfiler. Fatty acid metabolism-related DEGs (FAMDEGs) were further identified and analyzed. Machine learning algorithms, including Lasso (least absolute shrinkage and selection operator), support vector machine, and random forest algorithms, were utilized to identify hub FAMDEGs with the ability to predict ED occurrence. Coexpression analysis and gene set enrichment analysis of hub FAMDEGs were performed.

OUTCOME

Fatty acid metabolism-related functions (such as fatty acid metabolism and degradation) may play a vital role in ED.

RESULTS

In total, 5 hub FAMDEGs (, , , , and ) were identified and found to be differentially expressed between ED and normal samples. Gene set enrichment analysis identified key pathways associated with these genes. The area under the curve values of the 5 hub FAMDEGs for predicting ED occurrence were all >0.8.

CLINICAL TRANSLATION

Our results suggest that these 5 key FAMDEGs may serve as biomarkers for the diagnosis and treatment of ED.

STRENGTHS AND LIMITATIONS

The strengths of our study include the use of multiple datasets and machine learning algorithms to identify key FAMDEGs. However, limitations include the lack of validation in animal models and human tissues, as well as research on the mechanisms of these FAMDEGs.

CONCLUSION

Five hub FAMDEGs were identified as potential biomarkers for ED progression. Our work may prove that fatty acid metabolism-related genes are worth further investigation in ED.

摘要

背景

勃起功能障碍(ED)是一种影响中老年男性的常见病症。

目的

本研究旨在调查脂肪酸代谢相关基因的差异表达及ED的分子机制。

方法

从基因表达综合数据库下载GSE2457和GSE31247的表达谱并合并。使用R包limma获得ED与正常样本之间的差异表达基因(DEG)。使用R包clusterProfiler对DEG进行基因本体论和京都基因与基因组百科全书富集分析。进一步鉴定和分析脂肪酸代谢相关DEG(FAMDEG)。利用包括套索(最小绝对收缩和选择算子)、支持向量机和随机森林算法在内的机器学习算法来识别具有预测ED发生能力的核心FAMDEG。对核心FAMDEG进行共表达分析和基因集富集分析。

结果

脂肪酸代谢相关功能(如脂肪酸代谢和降解)可能在ED中起重要作用。

结果

共鉴定出5个核心FAMDEG(, , , ,和 ),发现它们在ED与正常样本之间存在差异表达。基因集富集分析确定了与这些基因相关的关键途径。这5个核心FAMDEG预测ED发生的曲线下面积值均>0.8。

临床转化

我们的结果表明,这5个关键FAMDEG可能作为ED诊断和治疗的生物标志物。

优点与局限性

我们研究的优点包括使用多个数据集和机器学习算法来识别关键FAMDEG。然而,局限性包括缺乏在动物模型和人体组织中的验证,以及对这些FAMDEG机制的研究。

结论

5个核心FAMDEG被确定为ED进展的潜在生物标志物。我们的工作可能证明脂肪酸代谢相关基因在ED中值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce1/10960936/5f3daab99e2b/qfae011ga1.jpg

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