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Differential Interactome Proposes Subtype-Specific Biomarkers and Potential Therapeutics in Renal Cell Carcinomas
Although many studies have been conducted on single gene therapies in cancer patients, the reality is that tumor arises from different coordinating protein groups. Unveiling perturbations in protein interactome related to the tumor formation may contribute to the development of effective diagnosis,...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926666/ https://www.ncbi.nlm.nih.gov/pubmed/33672271 http://dx.doi.org/10.3390/jpm11020158 |
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author | Caliskan, Aysegul Gulfidan, Gizem Sinha, Raghu Arga, Kazim Yalcin |
author_facet | Caliskan, Aysegul Gulfidan, Gizem Sinha, Raghu Arga, Kazim Yalcin |
author_sort | Caliskan, Aysegul |
collection | PubMed |
description | Although many studies have been conducted on single gene therapies in cancer patients, the reality is that tumor arises from different coordinating protein groups. Unveiling perturbations in protein interactome related to the tumor formation may contribute to the development of effective diagnosis, treatment strategies, and prognosis. In this study, considering the clinical and transcriptome data of three Renal Cell Carcinoma (RCC) subtypes (ccRCC, pRCC, and chRCC) retrieved from The Cancer Genome Atlas (TCGA) and the human protein interactome, the differential protein–protein interactions were identified in each RCC subtype. The approach enabled the identification of differentially interacting proteins (DIPs) indicating prominent changes in their interaction patterns during tumor formation. Further, diagnostic and prognostic performances were generated by taking into account DIP clusters which are specific to the relevant subtypes. Furthermore, considering the mesenchymal epithelial transition (MET) receptor tyrosine kinase (PDB ID: 3DKF) as a potential drug target specific to pRCC, twenty-one lead compounds were identified through virtual screening of ZINC molecules. In this study, we presented remarkable findings in terms of early diagnosis, prognosis, and effective treatment strategies, that deserve further experimental and clinical efforts. |
format | Online Article Text |
id | pubmed-7926666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79266662021-03-04 Differential Interactome Proposes Subtype-Specific Biomarkers and Potential Therapeutics in Renal Cell Carcinomas Caliskan, Aysegul Gulfidan, Gizem Sinha, Raghu Arga, Kazim Yalcin J Pers Med Article Although many studies have been conducted on single gene therapies in cancer patients, the reality is that tumor arises from different coordinating protein groups. Unveiling perturbations in protein interactome related to the tumor formation may contribute to the development of effective diagnosis, treatment strategies, and prognosis. In this study, considering the clinical and transcriptome data of three Renal Cell Carcinoma (RCC) subtypes (ccRCC, pRCC, and chRCC) retrieved from The Cancer Genome Atlas (TCGA) and the human protein interactome, the differential protein–protein interactions were identified in each RCC subtype. The approach enabled the identification of differentially interacting proteins (DIPs) indicating prominent changes in their interaction patterns during tumor formation. Further, diagnostic and prognostic performances were generated by taking into account DIP clusters which are specific to the relevant subtypes. Furthermore, considering the mesenchymal epithelial transition (MET) receptor tyrosine kinase (PDB ID: 3DKF) as a potential drug target specific to pRCC, twenty-one lead compounds were identified through virtual screening of ZINC molecules. In this study, we presented remarkable findings in terms of early diagnosis, prognosis, and effective treatment strategies, that deserve further experimental and clinical efforts. MDPI 2021-02-23 /pmc/articles/PMC7926666/ /pubmed/33672271 http://dx.doi.org/10.3390/jpm11020158 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Caliskan, Aysegul Gulfidan, Gizem Sinha, Raghu Arga, Kazim Yalcin Differential Interactome Proposes Subtype-Specific Biomarkers and Potential Therapeutics in Renal Cell Carcinomas |
title | Differential Interactome Proposes Subtype-Specific Biomarkers and Potential Therapeutics in Renal Cell Carcinomas |
title_full | Differential Interactome Proposes Subtype-Specific Biomarkers and Potential Therapeutics in Renal Cell Carcinomas |
title_fullStr | Differential Interactome Proposes Subtype-Specific Biomarkers and Potential Therapeutics in Renal Cell Carcinomas |
title_full_unstemmed | Differential Interactome Proposes Subtype-Specific Biomarkers and Potential Therapeutics in Renal Cell Carcinomas |
title_short | Differential Interactome Proposes Subtype-Specific Biomarkers and Potential Therapeutics in Renal Cell Carcinomas |
title_sort | differential interactome proposes subtype-specific biomarkers and potential therapeutics in renal cell carcinomas |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926666/ https://www.ncbi.nlm.nih.gov/pubmed/33672271 http://dx.doi.org/10.3390/jpm11020158 |
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