Department of Urology, Tangshan Central Hospital, Tangshan, China.
Kidney Blood Press Res. 2021;46(6):702-713. doi: 10.1159/000518437. Epub 2021 Oct 11.
Kidney renal clear cell carcinoma (KIRC) is a common cancer with high morbidity and mortality in renal cancer. Thus, the transcriptome data of KIRC patients in The Cancer Genome Atlas (TCGA) database were analyzed and drug candidates for the treatment of KIRC were explored through the connectivity map (CMap) database.
The transcriptome data of KIRC patients were downloaded from TCGA database, and KIRC-associated hub genes were screened out through differential analysis and protein-protein interaction (PPI) network analysis. Afterward, the CMap database was used to select drug candidates for KIRC treatment, and the drug-targeted genes were obtained through the STITCH database. A PPI network was constructed by combining drug-targeted genes with hub genes that affected the pathogenesis of KIRC to obtain final hub genes. Finally, combining hub genes and KIRC-associated hub genes, the pathways affected by drugs were explored by pathway enrichment analysis.
A total of 2,312 differentially expressed genes were found in patients, which were concentrated in immune cell activity, cytokine, and chemokine secretion pathways. Drug screening disclosed 5 drug candidates for KIRC treatment: fedratinib, Ly344864, geldanamycin, AS-605240, and luminespib. Based on drug-targeted genes and KIRC-associated hub genes, 16 hub genes were screened out. Pathway enrichment analysis revealed that drugs mainly affected pathways such as neuroactive ligand pathways, cell adhesion, and chemokines.
The above results indicated that fedratinib, LY 344864, geldanamycin, AS-605240, and luminespib could be used as candidates for KIRC therapy. The findings from this study will make contributions to the treatment of KIRC in the future.
肾透明细胞癌（KIRC）是一种常见的癌症，在肾癌中发病率和死亡率都很高。因此，通过连接图谱（CMap）数据库分析癌症基因组图谱（TCGA）数据库中 KIRC 患者的转录组数据，探索治疗 KIRC 的药物候选物。
从 TCGA 数据库下载 KIRC 患者的转录组数据，通过差异分析和蛋白质-蛋白质相互作用（PPI）网络分析筛选出 KIRC 相关的枢纽基因。然后，使用 CMap 数据库选择治疗 KIRC 的药物候选物，并通过 STITCH 数据库获得药物靶向基因。通过将药物靶向基因与影响 KIRC 发病机制的枢纽基因相结合，构建 PPI 网络，得到最终的枢纽基因。最后，结合枢纽基因和 KIRC 相关的枢纽基因，通过通路富集分析探讨受药物影响的通路。
共发现 2312 个差异表达基因，这些基因主要集中在免疫细胞活性、细胞因子和趋化因子分泌通路。药物筛选发现 5 种治疗 KIRC 的药物候选物：fedratinib、Ly344864、geldanamycin、AS-605240 和 luminespib。基于药物靶向基因和 KIRC 相关的枢纽基因，筛选出 16 个枢纽基因。通路富集分析表明，药物主要影响神经活性配体通路、细胞黏附、趋化因子等通路。
上述结果表明，fedratinib、LY344864、geldanamycin、AS-605240 和 luminespib 可作为 KIRC 治疗的候选药物。本研究的结果将为今后治疗 KIRC 做出贡献。
