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High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs

The malignant phenotype of tumour cells is fuelled by changes in the expression of various transcription factors, including some of the well-studied proteins such as p53 and Myc. Despite significant progress made, little is known about several other transcription factors, including ELF4, and how the...

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Autores principales: Kafita, Doris, Daka, Victor, Nkhoma, Panji, Zulu, Mildred, Zulu, Ephraim, Tembo, Rabecca, Ngwira, Zifa, Mwaba, Florence, Sinkala, Musalula, Munsaka, Sody
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034723/
https://www.ncbi.nlm.nih.gov/pubmed/33836003
http://dx.doi.org/10.1371/journal.pone.0248984
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author Kafita, Doris
Daka, Victor
Nkhoma, Panji
Zulu, Mildred
Zulu, Ephraim
Tembo, Rabecca
Ngwira, Zifa
Mwaba, Florence
Sinkala, Musalula
Munsaka, Sody
author_facet Kafita, Doris
Daka, Victor
Nkhoma, Panji
Zulu, Mildred
Zulu, Ephraim
Tembo, Rabecca
Ngwira, Zifa
Mwaba, Florence
Sinkala, Musalula
Munsaka, Sody
author_sort Kafita, Doris
collection PubMed
description The malignant phenotype of tumour cells is fuelled by changes in the expression of various transcription factors, including some of the well-studied proteins such as p53 and Myc. Despite significant progress made, little is known about several other transcription factors, including ELF4, and how they help shape the oncogenic processes in cancer cells. To this end, we performed a bioinformatics analysis to facilitate a detailed understanding of how the expression variations of ELF4 in human cancers are related to disease outcomes and the cancer cell drug responses. Here, using ELF4 mRNA expression data of 9,350 samples from the Cancer Genome Atlas pan-cancer project, we identify two groups of patient’s tumours: those that expressed high ELF4 transcripts and those that expressed low ELF4 transcripts across 32 different human cancers. We uncover that patients segregated into these two groups are associated with different clinical outcomes. Further, we find that tumours that express high ELF4 mRNA levels tend to be of a higher-grade, afflict a significantly older patient population and have a significantly higher mutation burden. By analysing dose-response profiles to 397 anti-cancer drugs of 612 well-characterised human cancer cell lines, we discover that cell lines that expressed high ELF4 mRNA transcript are significantly less responsive to 129 anti-cancer drugs, and only significantly more response to three drugs: dasatinib, WH-4-023, and Ponatinib, all of which remarkably target the proto-oncogene tyrosine-protein kinase SRC and tyrosine-protein kinase ABL1. Collectively our analyses have shown that, across the 32 different human cancers, the patients afflicted with tumours that overexpress ELF4 tended to have a more aggressive disease that is also is more likely more refractory to most anti-cancer drugs, a finding upon which we could devise novel categorisation of patient tumours, treatment, and prognostic strategies.
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spelling pubmed-80347232021-04-15 High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs Kafita, Doris Daka, Victor Nkhoma, Panji Zulu, Mildred Zulu, Ephraim Tembo, Rabecca Ngwira, Zifa Mwaba, Florence Sinkala, Musalula Munsaka, Sody PLoS One Research Article The malignant phenotype of tumour cells is fuelled by changes in the expression of various transcription factors, including some of the well-studied proteins such as p53 and Myc. Despite significant progress made, little is known about several other transcription factors, including ELF4, and how they help shape the oncogenic processes in cancer cells. To this end, we performed a bioinformatics analysis to facilitate a detailed understanding of how the expression variations of ELF4 in human cancers are related to disease outcomes and the cancer cell drug responses. Here, using ELF4 mRNA expression data of 9,350 samples from the Cancer Genome Atlas pan-cancer project, we identify two groups of patient’s tumours: those that expressed high ELF4 transcripts and those that expressed low ELF4 transcripts across 32 different human cancers. We uncover that patients segregated into these two groups are associated with different clinical outcomes. Further, we find that tumours that express high ELF4 mRNA levels tend to be of a higher-grade, afflict a significantly older patient population and have a significantly higher mutation burden. By analysing dose-response profiles to 397 anti-cancer drugs of 612 well-characterised human cancer cell lines, we discover that cell lines that expressed high ELF4 mRNA transcript are significantly less responsive to 129 anti-cancer drugs, and only significantly more response to three drugs: dasatinib, WH-4-023, and Ponatinib, all of which remarkably target the proto-oncogene tyrosine-protein kinase SRC and tyrosine-protein kinase ABL1. Collectively our analyses have shown that, across the 32 different human cancers, the patients afflicted with tumours that overexpress ELF4 tended to have a more aggressive disease that is also is more likely more refractory to most anti-cancer drugs, a finding upon which we could devise novel categorisation of patient tumours, treatment, and prognostic strategies. Public Library of Science 2021-04-09 /pmc/articles/PMC8034723/ /pubmed/33836003 http://dx.doi.org/10.1371/journal.pone.0248984 Text en © 2021 Kafita et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kafita, Doris
Daka, Victor
Nkhoma, Panji
Zulu, Mildred
Zulu, Ephraim
Tembo, Rabecca
Ngwira, Zifa
Mwaba, Florence
Sinkala, Musalula
Munsaka, Sody
High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs
title High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs
title_full High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs
title_fullStr High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs
title_full_unstemmed High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs
title_short High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs
title_sort high elf4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034723/
https://www.ncbi.nlm.nih.gov/pubmed/33836003
http://dx.doi.org/10.1371/journal.pone.0248984
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