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Screening Novel Drug Candidates for Kidney Renal Clear Cell Carcinoma Treatment: A Study on Differentially Expressed Genes through the Connectivity Map Database.
- Source :
-
Kidney & blood pressure research [Kidney Blood Press Res] 2021; Vol. 46 (6), pp. 702-713. Date of Electronic Publication: 2021 Oct 11. - Publication Year :
- 2021
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Abstract
- Objective: 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.<br />Methods: 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.<br />Results: 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.<br />Conclusion: 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.<br /> (© 2021 The Author(s). Published by S. Karger AG, Basel.)
- Subjects :
- Benzoquinones pharmacology
Carbazoles pharmacology
Carcinoma, Renal Cell genetics
Drug Screening Assays, Antitumor
Fluorobenzenes pharmacology
Gene Expression Regulation, Neoplastic drug effects
Humans
Kidney Neoplasms genetics
Lactams, Macrocyclic pharmacology
Pyrrolidines pharmacology
Sulfonamides pharmacology
Transcriptome drug effects
Antineoplastic Agents pharmacology
Carcinoma, Renal Cell drug therapy
Drug Discovery
Kidney Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0143
- Volume :
- 46
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Kidney & blood pressure research
- Publication Type :
- Academic Journal
- Accession number :
- 34818247
- Full Text :
- https://doi.org/10.1159/000518437