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Comprehensive bioinformatics analysis of the TP53 signaling pathway in Wilms’ tumor
BACKGROUND: Differential expression of tumor protein 53 (TP53, or p53) has been observed in multiple cancers. However, the expression levels and prognostic role of TP53 signaling pathway genes in Wilms’ tumor (WT) have yet to be fully explored. METHODS: The expression levels of TP53 signaling pathwa...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607069/ https://www.ncbi.nlm.nih.gov/pubmed/33178760 http://dx.doi.org/10.21037/atm-20-6047 |
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author | He, Changjing Qin, Huatao Tang, Haizhou Yang, Di Li, Yufeng Huang, Zhenwen Zhang, Donghu Lv, Changheng |
author_facet | He, Changjing Qin, Huatao Tang, Haizhou Yang, Di Li, Yufeng Huang, Zhenwen Zhang, Donghu Lv, Changheng |
author_sort | He, Changjing |
collection | PubMed |
description | BACKGROUND: Differential expression of tumor protein 53 (TP53, or p53) has been observed in multiple cancers. However, the expression levels and prognostic role of TP53 signaling pathway genes in Wilms’ tumor (WT) have yet to be fully explored. METHODS: The expression levels of TP53 signaling pathway genes including TP53, mouse double minute 2 (MDM2), mouse double minute 4 (MDM4), cyclin-dependent kinase 2A (CDKN2A), cyclin-dependent kinase 2B (CDKN2B), and tumor suppressor p53-binding protein 1 (TP53BP1) in WT were analyzed using the Oncomine database. Aberration types, co-mutations, mutation locations, signaling pathways, and the prognostic role of TP53 in WT were investigated using cBioPortal. MicroRNA (miRNA) and transcription factor (TF) targets were identified with miRTarBase, miWalk, and ChIP-X Enrichment Analysis 3 (CheA3), respectively. A protein-protein network was constructed using GeneMANIA. The expression of TP53 signaling genes were confirmed in WT samples and normal kidney tissues using the Human Protein Atlas (HPA). Cancer Therapeutics Response Portal (CTRP) was used to analyze the small molecules potentially targeting TP53. RESULTS: TP53 was significantly expressed in the Cutcliffe Renal (P=0.010), but not in the Yusenko Renal (P=0.094). Meanwhile, MDM2 was significantly overexpressed in the Yusenko Renal (P=0.058), but not in the Cutcliffe Renal (P=0.058). The expression levels of MDM4 no significant difference between the tumor and normal tissue samples. The most common TP53 alteration was missense and the proportion of TP53 pathway-related mutations was 2.3%. Co-expressed genes included ZNF609 (zinc finger protein 609), WRAP53 (WD40-encoding RNA antisense to p53), CNOT2 (CC chemokine receptor 4-negative regulator of transcription 2), and CDH13 (cadherin 13). TP53 alterations indicated poor prognosis of WT (P=1.051e-4). The regulators of the TP53 pathway included miR-485-5p and TFs NR2F2 and KDM5B. The functions of TP53 signaling pathway were signal transduction in response to DNA damage and regulate the cell cycle. The small molecules targeting TP53 included PRIMA-1, RITA, SJ-172550, and SCH-529074. CONCLUSIONS: TP53 was found to be differentially expressed in WT tissues. TP53 mutations indicated poor outcomes of WT. Therefore, pifithrin-mu, PRIMA-1, RITA, SJ-172550, and SCH-529074 could be used in combination with traditional chemotherapy to treat WT. |
format | Online Article Text |
id | pubmed-7607069 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-76070692020-11-10 Comprehensive bioinformatics analysis of the TP53 signaling pathway in Wilms’ tumor He, Changjing Qin, Huatao Tang, Haizhou Yang, Di Li, Yufeng Huang, Zhenwen Zhang, Donghu Lv, Changheng Ann Transl Med Original Article BACKGROUND: Differential expression of tumor protein 53 (TP53, or p53) has been observed in multiple cancers. However, the expression levels and prognostic role of TP53 signaling pathway genes in Wilms’ tumor (WT) have yet to be fully explored. METHODS: The expression levels of TP53 signaling pathway genes including TP53, mouse double minute 2 (MDM2), mouse double minute 4 (MDM4), cyclin-dependent kinase 2A (CDKN2A), cyclin-dependent kinase 2B (CDKN2B), and tumor suppressor p53-binding protein 1 (TP53BP1) in WT were analyzed using the Oncomine database. Aberration types, co-mutations, mutation locations, signaling pathways, and the prognostic role of TP53 in WT were investigated using cBioPortal. MicroRNA (miRNA) and transcription factor (TF) targets were identified with miRTarBase, miWalk, and ChIP-X Enrichment Analysis 3 (CheA3), respectively. A protein-protein network was constructed using GeneMANIA. The expression of TP53 signaling genes were confirmed in WT samples and normal kidney tissues using the Human Protein Atlas (HPA). Cancer Therapeutics Response Portal (CTRP) was used to analyze the small molecules potentially targeting TP53. RESULTS: TP53 was significantly expressed in the Cutcliffe Renal (P=0.010), but not in the Yusenko Renal (P=0.094). Meanwhile, MDM2 was significantly overexpressed in the Yusenko Renal (P=0.058), but not in the Cutcliffe Renal (P=0.058). The expression levels of MDM4 no significant difference between the tumor and normal tissue samples. The most common TP53 alteration was missense and the proportion of TP53 pathway-related mutations was 2.3%. Co-expressed genes included ZNF609 (zinc finger protein 609), WRAP53 (WD40-encoding RNA antisense to p53), CNOT2 (CC chemokine receptor 4-negative regulator of transcription 2), and CDH13 (cadherin 13). TP53 alterations indicated poor prognosis of WT (P=1.051e-4). The regulators of the TP53 pathway included miR-485-5p and TFs NR2F2 and KDM5B. The functions of TP53 signaling pathway were signal transduction in response to DNA damage and regulate the cell cycle. The small molecules targeting TP53 included PRIMA-1, RITA, SJ-172550, and SCH-529074. CONCLUSIONS: TP53 was found to be differentially expressed in WT tissues. TP53 mutations indicated poor outcomes of WT. Therefore, pifithrin-mu, PRIMA-1, RITA, SJ-172550, and SCH-529074 could be used in combination with traditional chemotherapy to treat WT. AME Publishing Company 2020-10 /pmc/articles/PMC7607069/ /pubmed/33178760 http://dx.doi.org/10.21037/atm-20-6047 Text en 2020 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article He, Changjing Qin, Huatao Tang, Haizhou Yang, Di Li, Yufeng Huang, Zhenwen Zhang, Donghu Lv, Changheng Comprehensive bioinformatics analysis of the TP53 signaling pathway in Wilms’ tumor |
title | Comprehensive bioinformatics analysis of the TP53 signaling pathway in Wilms’ tumor |
title_full | Comprehensive bioinformatics analysis of the TP53 signaling pathway in Wilms’ tumor |
title_fullStr | Comprehensive bioinformatics analysis of the TP53 signaling pathway in Wilms’ tumor |
title_full_unstemmed | Comprehensive bioinformatics analysis of the TP53 signaling pathway in Wilms’ tumor |
title_short | Comprehensive bioinformatics analysis of the TP53 signaling pathway in Wilms’ tumor |
title_sort | comprehensive bioinformatics analysis of the tp53 signaling pathway in wilms’ tumor |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607069/ https://www.ncbi.nlm.nih.gov/pubmed/33178760 http://dx.doi.org/10.21037/atm-20-6047 |
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