Deng Wenjia, Cao Honggang, Sun Taotao, Yuan Penghui
Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Transl Androl Urol. 2025 Mar 30;14(3):791-807. doi: 10.21037/tau-2025-6. Epub 2025 Mar 26.
Diabetes mellitus-related erectile dysfunction (DMED) is characterized by complicated pathogenesis and unsatisfactory therapeutic remedies. Glycolysis plays an essential role in diabetic complications and whether it is involved in the process of DMED has not been expounded. The aim of this study was to investigate the genetic profiling of glycolysis and explore potential mechanisms for DMED.
Glycolysis-related genes (GRGs) and gene expression matrix of DMED were obtained from the molecular signatures database and gene expression omnibus dataset. Differentially expressed analysis and support vector machine-recursive feature elimination (SVM-RFE) method were both used to obtain hub GRGs. Interactive network and functional enrichment analyses were performed to clarify the associated biological roles of these genes. The expression profile of hub GRGs was validated in cavernous endothelial cells, animals, and clinical patients. The subpopulation distribution of hub GRGs was further identified. In addition, a miRNA-GRGs network was constructed and expression patterns as well as molecular functions of relevant miRNAs were explored and validated. In addition, the relationship between hypoxia and DMED was also uncovered.
Based on the combined analysis, 48 differentially expressed GRGs were obtained. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these genes were significantly enriched in carbon metabolism and oxidoreductase activities. Then hub GRGs including down-regulated as well as up-regulated genes in DMED were identified ultimately. Among them, , , and were well-validated. In addition, 334 glycolysis-related miRNAs were verified and they were involved in endoplasmic reticulum membrane activity, smooth muscle cell differentiation and angiogenesis. After validation of miRNA signature in DMED patients, miR-222-5p, let-7e-5p, miR-184, and miR-122-3p were identified as the promising glycolysis-related miRNA biomarkers in DMED.
We clarified the expression signature of GRGs in DMED based on multi-omics analysis for the first time. It will be significantly important to reveal pathological mechanisms and promising treatments in DMED.
糖尿病相关性勃起功能障碍（DMED）的发病机制复杂，治疗效果欠佳。糖酵解在糖尿病并发症中起重要作用，但其是否参与DMED的发病过程尚未阐明。本研究旨在探究糖酵解的基因图谱并探索DMED的潜在机制。
从分子特征数据库和基因表达综合数据集获取DMED的糖酵解相关基因（GRGs）和基因表达矩阵。采用差异表达分析和支持向量机递归特征消除（SVM-RFE）方法获取核心GRGs。进行交互网络和功能富集分析以阐明这些基因的相关生物学作用。在海绵体内皮细胞、动物和临床患者中验证核心GRGs的表达谱。进一步确定核心GRGs的亚群分布。此外，构建miRNA-GRGs网络，探索并验证相关miRNA的表达模式和分子功能。此外，还揭示了缺氧与DMED之间的关系。
基于联合分析，获得了48个差异表达的GRGs。基因本体论和京都基因与基因组百科全书富集分析表明，这些基因在碳代谢和氧化还原酶活性方面显著富集。最终确定了DMED中包括下调和上调基因的核心GRGs。其中， 、 和 得到了充分验证。此外，验证了334个与糖酵解相关的miRNA，它们参与内质网膜活性、平滑肌细胞分化和血管生成。在DMED患者中验证miRNA特征后，miR-222-5p, let-7e-5p, miR-184和miR-122-3p被确定为DMED中有前景的糖酵解相关miRNA生物标志物。
我们首次基于多组学分析阐明了DMED中GRGs的表达特征。这对于揭示DMED的病理机制和有前景的治疗方法具有重要意义。
