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Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma

It is well established that the PTEN (Phosphatase and Tensin Homolog) mutant is a frequently mutated gene found in clear cell renal cell carcinoma (ccRCC), making it a potential biomarker for individualized treatment opinions. Here, in the present study, we designed a method to evaluate the signific...

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Autores principales: Fan, Caibin, Zhao, Chunchun, Wang, Fei, Li, Shugen, Wang, Jianqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518664/
https://www.ncbi.nlm.nih.gov/pubmed/31139560
http://dx.doi.org/10.3389/fonc.2019.00357
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author Fan, Caibin
Zhao, Chunchun
Wang, Fei
Li, Shugen
Wang, Jianqing
author_facet Fan, Caibin
Zhao, Chunchun
Wang, Fei
Li, Shugen
Wang, Jianqing
author_sort Fan, Caibin
collection PubMed
description It is well established that the PTEN (Phosphatase and Tensin Homolog) mutant is a frequently mutated gene found in clear cell renal cell carcinoma (ccRCC), making it a potential biomarker for individualized treatment opinions. Here, in the present study, we designed a method to evaluate the significance of the PTEN mutation in the prognosis and drug selection of ccRCC, determine the potential changing pathways and genes associated with the mechanisms. The most recent TCGA data shows that the PTEN mutation is found in 5% of ccRCC patients. In total, 2,569 genes were identified as DEGs. GO and KEGG analysis suggested that DEGs were significantly enriched in categories associated with cell division and multiple metabolic progressions. The top 10 genes, ranked by degree, were identified as hub genes from the protein–protein interaction network (PPI). What is more, patients with the PTEN mutation were associated with a worsened prognosis of ccRCC. Data from the GDSC database indicated that the selective AKT inhibitor, GSK690693, is a selective inhibitor for ccRCC with the PTEN mutation. Our findings have indicated that multiple genes and pathways may play a crucial role in PTEN mutation ccRCC, offering candidate targets and strategies for PTEN mutation ccRCC individualized treatment.
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spelling pubmed-65186642019-05-28 Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma Fan, Caibin Zhao, Chunchun Wang, Fei Li, Shugen Wang, Jianqing Front Oncol Oncology It is well established that the PTEN (Phosphatase and Tensin Homolog) mutant is a frequently mutated gene found in clear cell renal cell carcinoma (ccRCC), making it a potential biomarker for individualized treatment opinions. Here, in the present study, we designed a method to evaluate the significance of the PTEN mutation in the prognosis and drug selection of ccRCC, determine the potential changing pathways and genes associated with the mechanisms. The most recent TCGA data shows that the PTEN mutation is found in 5% of ccRCC patients. In total, 2,569 genes were identified as DEGs. GO and KEGG analysis suggested that DEGs were significantly enriched in categories associated with cell division and multiple metabolic progressions. The top 10 genes, ranked by degree, were identified as hub genes from the protein–protein interaction network (PPI). What is more, patients with the PTEN mutation were associated with a worsened prognosis of ccRCC. Data from the GDSC database indicated that the selective AKT inhibitor, GSK690693, is a selective inhibitor for ccRCC with the PTEN mutation. Our findings have indicated that multiple genes and pathways may play a crucial role in PTEN mutation ccRCC, offering candidate targets and strategies for PTEN mutation ccRCC individualized treatment. Frontiers Media S.A. 2019-05-08 /pmc/articles/PMC6518664/ /pubmed/31139560 http://dx.doi.org/10.3389/fonc.2019.00357 Text en Copyright © 2019 Fan, Zhao, Wang, Li and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Fan, Caibin
Zhao, Chunchun
Wang, Fei
Li, Shugen
Wang, Jianqing
Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma
title Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma
title_full Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma
title_fullStr Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma
title_full_unstemmed Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma
title_short Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma
title_sort significance of pten mutation in cellular process, prognosis, and drug selection in clear cell renal cell carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518664/
https://www.ncbi.nlm.nih.gov/pubmed/31139560
http://dx.doi.org/10.3389/fonc.2019.00357
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