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Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors
BACKGROUND: The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this stud...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617821/ https://www.ncbi.nlm.nih.gov/pubmed/37027423 http://dx.doi.org/10.1097/CM9.0000000000002343 |
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author | Li, Xinyu Ma, Weining Liu, Hui Wang, Deming Su, Lixin Yang, Xitao |
author_facet | Li, Xinyu Ma, Weining Liu, Hui Wang, Deming Su, Lixin Yang, Xitao |
author_sort | Li, Xinyu |
collection | PubMed |
description | BACKGROUND: The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication. METHODS: Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)–messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard. RESULTS: Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A. In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression (P <0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs. CONCLUSIONS: This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents. |
format | Online Article Text |
id | pubmed-10617821 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-106178212023-11-05 Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors Li, Xinyu Ma, Weining Liu, Hui Wang, Deming Su, Lixin Yang, Xitao Chin Med J (Engl) Original Articles BACKGROUND: The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication. METHODS: Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)–messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard. RESULTS: Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A. In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression (P <0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs. CONCLUSIONS: This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents. Lippincott Williams & Wilkins 2023-11-05 2023-03-28 /pmc/articles/PMC10617821/ /pubmed/37027423 http://dx.doi.org/10.1097/CM9.0000000000002343 Text en Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
spellingShingle | Original Articles Li, Xinyu Ma, Weining Liu, Hui Wang, Deming Su, Lixin Yang, Xitao Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors |
title | Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors |
title_full | Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors |
title_fullStr | Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors |
title_full_unstemmed | Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors |
title_short | Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors |
title_sort | integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617821/ https://www.ncbi.nlm.nih.gov/pubmed/37027423 http://dx.doi.org/10.1097/CM9.0000000000002343 |
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