研究动态
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通过生物信息学分析和逆向网络药理学,鉴定清除细胞肾细胞癌的潜在生物标志物及候选治疗药物。

Identification of potential biomarkers and candidate therapeutic drugs for clear cell renal cell carcinoma by bioinformatic analysis and reverse network pharmacology.

发表日期:2023 Sep 01
作者: Zhuo Meng, Bo Yuan, Shuang Yang, Xiaotong Fu, Baoyue Zhang, Kun Xu, Pengfei Bao, Youliang Huang
来源: MOLECULAR & CELLULAR PROTEOMICS

摘要:

本研究旨在利用生物信息学技术分析潜在的生物标志物,探索清除型肾细胞癌(ccRCC)的发病机制,并调查中国传统草药成分的潜在应用,为ccRCC的早期诊断和有效治疗提供理论依据。我们从基因表达测序集GSE6344和GSE53757数据库中获取相关数据,筛选出参与ccRCC致癌和疾病进展的差异表达基因(DEGs)。我们使用相关软件和在线分析平台进行富集分析、蛋白质相互作用网络构建、生存分析和草药筛选。此外,我们还进行了网络药理学分析,筛选出ccRCC潜在靶点药物,并使用分子对接分析验证其效果。通过上述过程,我们共提取了274个共同的DEGs,其中包括194个上调基因和80个下调基因。富集分析表明,DEGs主要与多种氨基酸代谢和HIF信号通路相关。我们筛选出了FLT1、BDNF、LCP2、AGXT2、PLG、SLC13A3、SLC47A2、SLC22A8、SLC22A7和SLC22A7等十个核心基因。生存分析显示FLT1、BDNF、AGXT2、PLG、SLC47A2、SLC22A8和SLC12A3与ccRCC的整体生存密切相关,而AGXT2、SLC47A2、SLC22A8和SLC22A7与疾病自由生存密切相关。我们筛选出的潜在治疗草药包括丹参、白果、银杏、黄芩和穿山龙。可能在ccRCC治疗中发挥效果的活性化合物包括山奈酚、蓝钟素A和(-)表没食子酸。2023年版权归作者所有。由Wolters Kluwer Health出版。
This study aims to analyze the potential biomarkers using bioinformatics technology, explore the pathogenesis, and investigate potential Chinese herbal ingredients for the Clear cell renal cell carcinoma (ccRCC), which could provide theoretical basis for early diagnosis and effective treatment of ccRCC. The gene expression datasets GSE6344 and GSE53757 were obtained from the Gene Expression Omnibus database to screen differentially expressed genes (DEGs) involved in ccRCC carcinogenesis and disease progression. Enrichment analyses, protein-protein interaction networks construction, survival analysis and herbal medicines screening were performed with related software and online analysis platforms. Moreover, network pharmacology analysis has also been performed to screen potential target drugs of ccRCC and molecular docking analysis has been used to validate their effects. Total 274 common DEGs were extracted through above process, including 194 up-regulated genes and 80 down-regulated genes. The enrichment analysis revealed that DEGs were significantly focused on multiple amino acid metabolism and HIF signaling pathway. Ten hub genes, including FLT1, BDNF, LCP2, AGXT2, PLG, SLC13A3, SLC47A2, SLC22A8, SLC22A7, and SLC13A3, were screened. Survival analysis showed that FLT1, BDNF, AGXT2, PLG, SLC47A2, SLC22A8, and SLC12A3 were closely correlated with the overall survival of ccRCC, and AGXT2, SLC47A2, SLC22A8, and SLC22A7 were closely associated with DFS. The potential therapeutic herbs that have been screened were Danshen, Baiguo, Yinxing, Huangqin and Chuanshanlong. The active compounds which may be effective in ccRCC treatment were kaempferol, Scillaren A and (-)-epigallocatechin-3-gallate.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.