Yue Dong, Dong Fengyun, Wang Sen, Zheng Miao
Department of Urology, Affiliated Hospital of Jining Medical University, Jining, China.
Department of Clinical Laboratory, Affiliated Hospital of Jining Medical University, Jining, China.
Sci Rep. 2025 Jun 5;15(1):19736. doi: 10.1038/s41598-025-03102-8.
The defective function of succinate dehydrogenase promotes the development and progression of kidney renal clear cell renal cell carcinoma (ccRCC). However, the molecular mechanism of succinate metabolism-related genes (SMRGs) has not been extensively studied in KIRC. First, differentially expressed SMRGs (DE-SMRGs) were screened among genesets. Next, functional enrichment analysis was performed to investigate the functions of DE-SMRGs. The univariate Cox algorithm, LASSO, and multivariate Cox analysis were performed to obtain biomarkers and build a prognostic model. Afterward, enrichment and immune microenvironment analysis were carried out in two different risk subgroups. Finally, expression validation and expression intensity of prognostic gene was verified by in situ and in vitro experiments. In total, 138 DE-SMRGs were screened by overlapping SMRGs and differentially expressed genes. The functional enrichment results revealed that DE-SMRGs were implicated in retinoic acid metabolic process and retinol metabolism. Then, 8 succinate metabolism-related biomarkers were obtained, and prognostic model was developed and SLC25A4 ranked the highest in importance. SLC25A4 was down-regulated in KIRC, and its upregulation was related to better overall survival in patients from public datasets and in clinical cases. SLC25A4 attenuated cell proliferation, cell invasion, and exerted its biological function by inhibiting the STAT3 signaling pathway. Our study reveals that succinate metabolism-related biomarkers can provide a basis for exploring the prediction of prognosis in ccRCC.
琥珀酸脱氢酶的功能缺陷促进肾透明细胞癌(ccRCC)的发生发展。然而,琥珀酸代谢相关基因(SMRGs)在肾透明细胞癌(KIRC)中的分子机制尚未得到广泛研究。首先,在基因集中筛选差异表达的SMRGs(DE-SMRGs)。其次,进行功能富集分析以研究DE-SMRGs的功能。采用单因素Cox算法、LASSO和多因素Cox分析来获得生物标志物并建立预后模型。随后,在两个不同风险亚组中进行富集和免疫微环境分析。最后,通过原位和体外实验验证预后基因的表达及表达强度。通过重叠SMRGs和差异表达基因,共筛选出138个DE-SMRGs。功能富集结果显示,DE-SMRGs与视黄酸代谢过程和视黄醇代谢有关。然后,获得了8个与琥珀酸代谢相关的生物标志物,建立了预后模型,其中SLC25A4的重要性排名最高。SLC25A4在KIRC中表达下调,其上调与公共数据集和临床病例中患者更好的总生存期相关。SLC25A4通过抑制STAT3信号通路减弱细胞增殖和细胞侵袭,并发挥其生物学功能。我们的研究表明,琥珀酸代谢相关生物标志物可为探索ccRCC预后预测提供依据。
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