Screening Novel Drug Candidates for Kidney Renal Clear Cell Carcinoma Treatment: A Study on Differentially Expressed Genes through the Connectivity Map Database

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 con...

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Autores principales:	Bin Gao, Lijuan Wang, Na Zhang, Miaomiao Han, Yubo Zhang, Huancai Liu, Dongli Sun, Yifei Liu
Formato:	article
Lenguaje:	EN
Publicado:	Karger Publishers 2021
Materias:	kidney renal clear cell carcinoma connectivity map drug screening the cancer genome atlas Dermatology RL1-803 Diseases of the circulatory (Cardiovascular) system RC666-701 Diseases of the genitourinary system. Urology RC870-923
Acceso en línea:	https://doaj.org/article/f7d30c6ae72b429b8215d369bf3fb181
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spelling	oai:doaj.org-article:f7d30c6ae72b429b8215d369bf3fb1812021-11-11T10:40:44ZScreening Novel Drug Candidates for Kidney Renal Clear Cell Carcinoma Treatment: A Study on Differentially Expressed Genes through the Connectivity Map Database1420-40961423-014310.1159/000518437https://doaj.org/article/f7d30c6ae72b429b8215d369bf3fb1812021-10-01T00:00:00Zhttps://www.karger.com/Article/FullText/518437https://doaj.org/toc/1420-4096https://doaj.org/toc/1423-0143Objective: 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. 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. 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. 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.Bin GaoLijuan WangNa ZhangMiaomiao HanYubo ZhangHuancai LiuDongli SunYifei LiuKarger Publishersarticlekidney renal clear cell carcinomaconnectivity mapdrug screeningthe cancer genome atlasDermatologyRL1-803Diseases of the circulatory (Cardiovascular) systemRC666-701Diseases of the genitourinary system. UrologyRC870-923ENKidney & Blood Pressure Research, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	kidney renal clear cell carcinoma connectivity map drug screening the cancer genome atlas Dermatology RL1-803 Diseases of the circulatory (Cardiovascular) system RC666-701 Diseases of the genitourinary system. Urology RC870-923
spellingShingle	kidney renal clear cell carcinoma connectivity map drug screening the cancer genome atlas Dermatology RL1-803 Diseases of the circulatory (Cardiovascular) system RC666-701 Diseases of the genitourinary system. Urology RC870-923 Bin Gao Lijuan Wang Na Zhang Miaomiao Han Yubo Zhang Huancai Liu Dongli Sun Yifei Liu Screening Novel Drug Candidates for Kidney Renal Clear Cell Carcinoma Treatment: A Study on Differentially Expressed Genes through the Connectivity Map Database
description	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. 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. 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. 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.
format	article
author	Bin Gao Lijuan Wang Na Zhang Miaomiao Han Yubo Zhang Huancai Liu Dongli Sun Yifei Liu
author_facet	Bin Gao Lijuan Wang Na Zhang Miaomiao Han Yubo Zhang Huancai Liu Dongli Sun Yifei Liu
author_sort	Bin Gao
title	Screening Novel Drug Candidates for Kidney Renal Clear Cell Carcinoma Treatment: A Study on Differentially Expressed Genes through the Connectivity Map Database
title_short	Screening Novel Drug Candidates for Kidney Renal Clear Cell Carcinoma Treatment: A Study on Differentially Expressed Genes through the Connectivity Map Database
title_full	Screening Novel Drug Candidates for Kidney Renal Clear Cell Carcinoma Treatment: A Study on Differentially Expressed Genes through the Connectivity Map Database
title_fullStr	Screening Novel Drug Candidates for Kidney Renal Clear Cell Carcinoma Treatment: A Study on Differentially Expressed Genes through the Connectivity Map Database
title_full_unstemmed	Screening Novel Drug Candidates for Kidney Renal Clear Cell Carcinoma Treatment: A Study on Differentially Expressed Genes through the Connectivity Map Database
title_sort	screening novel drug candidates for kidney renal clear cell carcinoma treatment: a study on differentially expressed genes through the connectivity map database
publisher	Karger Publishers
publishDate	2021
url	https://doaj.org/article/f7d30c6ae72b429b8215d369bf3fb181
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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

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