局灶节段性肾小球硬化分子标志物鉴定及其潜在治疗药物预测
Identification of Molecular Markers and Prediction of Potential Therapeutic Drugs for Focal Segmental Glomurular Sclerosis
DOI: 10.12677/hjcb.2025.153003, PDF,    科研立项经费支持
作者: 张苗苗*, 辜澜涛, 韦思慧, 林 军, 吴群英#：桂林医科大学智能医学与生物技术学院，广西 桂林；桂林医科大学广西高校分子医学工程重点实验室，广西 桂林；李康慧*：桂林医科大学附属医院肾内科，广西 桂林；张 扬：深圳市坪山区人民医院检验科，广东 深圳
关键词: 局灶节段性肾小球硬化；生物信息学；分子标志物；小分子药物；分子对接；Focal Segmental Glomurular Sclerosis； Bioinformatics； Molecular Markers； Small Molecule Drugs； Molecular Docking
摘要: 利用生物信息学分析方法鉴定局灶节段性肾小球硬化(Focal Segmental Glomurular Sclerosis, FSGS)相关的分子标志物，并预测其潜在的治疗药物。从GEO数据库下载FSGS相关的基因表达谱芯片数据集，利用R语言筛选差异表达基因(DEGs)，对DEGs进行功能富集分析和蛋白质–蛋白质相互作用(PPI)网络分析，利用Cytocape软件筛选关键基因，通过验证集验证其表达水平和诊断价值；使用CIBERSORT反卷积算法进行免疫细胞浸润分析；结合HPA数据库的单细胞测序数据和GeneCards数据库分析关键基因的表达和亚细胞定位；利用CMap数据库和分子对接方法预测和验证潜在治疗FSGS的小分子药物。一共获得111个DEGs，KEGG富集分析表明，这些DEGs主要参与有毒物质反应、解毒和JAK-STAT调控受体信号通路等。通过生物信息学分析，确定了EGF和HDAC5是FSGS相关的关键基因，ROC分析证实两者均具有较高的诊断效能。1-苯基双胍、水仙环素和花萼海绵诱癌素可能是潜在治疗FSGS的小分子药物。本研究鉴定了FSGS相关的关键基因及其潜在的治疗药物，为FSGS患者的临床诊断和治疗提供了新思路。
Abstract: Bioinformatics analysis was used to identify molecular markers associated with Focal Segmental Glomurular Sclerosis (FSGS) and predict potential therapeutic agents. Gene expression microarray datasets associated with FSGS were downloaded from the GEO database. Differentially Expressed Genes (DEGs) were identified using R language and subjected to functional enrichment analysis and Protein-Protein Interaction (PPI) network analysis. Key genes were selected using Cytoscape software, and their expression levels and diagnostic value were validated using validation sets. Immune cell infiltration analysis was conducted using the CIBERSORT deconvolution algorithm. The expression and subcellular localization of key genes were analyzed in conjunction with single-cell sequencing data from the HPA database and information from the GeneCards database. Potential small-molecule drugs for treating FSGS were predicted and validated using the CMap database and molecular docking methods. Expression patterns and subcellular localizations of the key genes were analyzed by combining single-cell sequencing data from the HPA database with information from the GeneCards database. Potential small-molecule drugs for the treatment of FSGS were predicted using the CMap database and validated through molecular docking methods. A total of 111 DEGs were identified. KEGG enrichment analyses revealed that these DEGs were mainly involved in toxic response, detoxification, and JAK-STAT-regulated receptor signaling pathway. Through bioinformatics analysis, EGF and HDAC5 were determined to be key hub genes associated with FSGS, and ROC analysis confirmed that both genes exhibit high diagnostic efficacy. Additionally, 1-phenylbiguanide, narciclasine, and calyculin were predicted to be potential small-molecule drugs for the treatment of FSGS. This study identified key genes and potential therapeutic drugs associated with FSGS, providing new insights for the clinical diagnosis and treatment of FSGS patients.
文章引用：张苗苗, 李康慧, 辜澜涛, 张扬, 韦思慧, 林军, 吴群英. 局灶节段性肾小球硬化分子标志物鉴定及其潜在治疗药物预测[J]. 计算生物学, 2025, 15(3): 25-35. https://doi.org/10.12677/hjcb.2025.153003

参考文献

[1] 王羽, 吴超, 汪裕伟, 等. 原发性局灶节段性肾小球硬化症的病理亚型与临床疗效的相关性分析[J]. 沈阳医学院学报, 2023, 25(3): 238-242.
[2] 张小田, 周国平. TFAP2A对肾小球硬化相关基因NPHS2的转录调控作用观察[J]. 山东医药, 2023, 63(32): 20-24.
[3] 匡仟卉柠, 高春林, 姚俊, 等. 局灶节段性肾小球硬化诊治现状[J]. 临床儿科杂志, 2019, 37(6): 470-474.
[4] Zhang, Y.X., Bai, J.Y., Pu, X., Lv, J. and Dai, E.L. (2023) An Integrated Bioinformatics Approach to Identify Key Biomarkers in the Tubulointerstitium of Patients with Focal Segmental Glomerulosclerosis and Construction of mRNA-miRNA-lncRNA/circRNA Networks. Renal Failure, 45, Article ID: 2284212. [Google Scholar] [CrossRef] [PubMed]
[5] Bai, J., Pu, X., Zhang, Y. and Dai, E. (2022) Renal Tubular Gene Biomarkers Identification Based on Immune Infiltrates in Focal Segmental Glomerulosclerosis. Renal Failure, 44, 966-986. [Google Scholar] [CrossRef] [PubMed]
[6] Zhang, Y.X., Lv, J., Bai, J.Y., Pu, X. and Dai, E.L. (2023) Identification of Key Biomarkers of the Glomerulus in Focal Segmental Glomerulosclerosis and Their Relationship with Immune Cell Infiltration Based on WGCNA and the LASSO Algorithm. Renal Failure, 45, Article ID: 2202264. [Google Scholar] [CrossRef] [PubMed]
[7] Gholaminejad, A., Ghaeidamini, M., Simal-Gandara, J. and Roointan, A. (2022) An Integrative in Silico Study to Discover Key Drivers in Pathogenicity of Focal and Segmental Glomerulosclerosis. Kidney and Blood Pressure Research, 47, 410-422. [Google Scholar] [CrossRef] [PubMed]
[8] 高言, 张嘉欣, 赵静, 谢席胜. 基于足细胞病研究看原发性FSGS诊治新进展[J]. 中国中西医结合肾病杂志, 2024, 25(11): 1028-1031.
[9] Deng, Y., Liu, K., Qiu, Q., Tang, Z., Que, R., Li, D., et al. (2023) Identification and Validation of Hub Genes in Drug Induced Acute Kidney Injury Basing on Integrated Transcriptomic Analysis. Frontiers in Immunology, 14, Article 1126348. [Google Scholar] [CrossRef] [PubMed]
[10] 徐丽辰, 李贵森. 局灶节段性肾小球硬化发病机制及治疗进展[J]. 内科理论与实践, 2023, 18(5): 363-367.
[11] 张碧丽, 李志军, 宋兰云, 等. Desmin蛋白与局灶节段性肾小球硬化的相关性研究[J]. 临床儿科杂志, 2009, 27(1): 76-78.
[12] Lv, C., Wu, X., Wang, X., Su, J., Zeng, H., Zhao, J., et al. (2017) The Gene Expression Profiles in Response to 102 Traditional Chinese Medicine (TCM) Components: A General Template for Research on TCMs. Scientific Reports, 7, Article No. 352. [Google Scholar] [CrossRef] [PubMed]
[13] 徐子斌. 精准化5/6肾切除术建立局灶节段性肾小球硬化模型观察JAK2/STAT3信号通路的变化[D]: [硕士学位论文]. 广州: 南方医科大学, 2023.
[14] Hall, G., Lane, B.M., Khan, K., Pediaditakis, I., Xiao, J., Wu, G., et al. (2018) The Human FSGS-Causing ANLN R431C Mutation Induces Dysregulated PI3K/AKT/mTOR/Rac1 Signaling in Podocytes. Journal of the American Society of Nephrology, 29, 2110-2122. [Google Scholar] [CrossRef] [PubMed]
[15] 王娟, 王乐, 毛加荣, 等. 中医药靶向JAK/STAT信号通路防治IgA肾病的研究进展[J]. 中国中西医结合肾病杂志, 2024, 25(2): 171-173+182.
[16] Hou, Y.P., Diao, T.T., Xu, Z.H., Mao, X., Wang, C. and Li, B. (2022) Bioinformatic Analysis Combined with Experimental Validation Reveals Novel Hub Genes and Pathways Associated with Focal Segmental Glomerulosclerosis. Frontiers in Molecular Biosciences, 8, Article 691966. [Google Scholar] [CrossRef] [PubMed]
[17] Dong, Z., Chen, F., Peng, S., Liu, X., Liu, X., Guo, L., et al. (2023) Identification of the Key Immune-Related Genes and Immune Cell Infiltration Changes in Renal Interstitial Fibrosis. Frontiers in Endocrinology, 14, Article 1207444. [Google Scholar] [CrossRef] [PubMed]
[18] 邓芳静, 朱杰夫, 吴雄飞. 组蛋白去乙酰化酶在急性肾损伤中的研究进展[J]. 临床肾脏病杂志, 2022, 22(4): 333-338.
[19] 许朝霞. 组蛋白去乙酰化酶5对糖尿病肾小管上皮细胞转分化的影响及机制[D]: [硕士学位论文]. 石家庄: 河北医科大学, 2020.
[20] Xiao, A., Chen, X., Ma, J., Chen, X., Long, T., Ma, Y., et al. (2025) Gene Signature-Guided Drug Screening Identified Narciclasine as a Potential Therapeutic for Interstitial Fibrosis of the Kidney. Kidney International, 108, 74-89. [Google Scholar] [CrossRef] [PubMed]
[21] Yin, L., Huang, X., Zhang, B., Zhu, Q. and Zhao, H. (2025) Narciclasine Attenuates Sepsis-Associated Acute Kidney Injury through the ESR1/S100A11 Axis. Functional & Integrative Genomics, 25, Article No. 13. [Google Scholar] [CrossRef] [PubMed]

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