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A Bioinformatics Evaluation of the Role of Dual-Specificity Tyrosine-Regulated Kinases in Colorectal Cancer

SIMPLE SUMMARY: The dual-specificity tyrosine-regulated kinase (DYRK) family has been implicated in various diseases, including cancer. However, its role in colorectal cancer has not been elucidated. In this research, we used publicly available web-based tools to investigate DYRKs status in colorect...

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Autores principales: Laham, Amina Jamal, El-Awady, Raafat, Lebrun, Jean-Jacques, Ayad, Maha Saber
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025863/
https://www.ncbi.nlm.nih.gov/pubmed/35454940
http://dx.doi.org/10.3390/cancers14082034
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author Laham, Amina Jamal
El-Awady, Raafat
Lebrun, Jean-Jacques
Ayad, Maha Saber
author_facet Laham, Amina Jamal
El-Awady, Raafat
Lebrun, Jean-Jacques
Ayad, Maha Saber
author_sort Laham, Amina Jamal
collection PubMed
description SIMPLE SUMMARY: The dual-specificity tyrosine-regulated kinase (DYRK) family has been implicated in various diseases, including cancer. However, its role in colorectal cancer has not been elucidated. In this research, we used publicly available web-based tools to investigate DYRKs status in colorectal cancer. Our results showed that among DYRKs, only DYRK1A was upregulated significantly in late tumor stages, and it is associated with poor prognosis for colorectal cancer patients. These finding comprehensively characterized DYRK1A as a potential new therapeutic approach in CRC, especially in late tumor stages. ABSTRACT: Colorectal cancer (CRC) is the third most common cancer worldwide and has an increasing incidence in younger populations. The dual-specificity tyrosine-regulated kinase (DYRK) family has been implicated in various diseases, including cancer. However, the role and contribution of the distinct family members in regulating CRC tumorigenesis has not been addressed yet. Herein, we used publicly available CRC patient datasets (TCGA RNA sequence) and several bioinformatics webtools to perform in silico analysis (GTEx, GENT2, GEPIA2, cBioPortal, GSCALite, TIMER2, and UALCAN). We aimed to investigate the DYRK family member expression pattern, prognostic value, and oncological roles in CRC. This study shed light on the role of distinct DYRK family members in CRC and their potential outcome predictive value. Based on mRNA level, DYRK1A is upregulated in late tumor stages, with lymph node and distant metastasis. All DYRKs were found to be implicated in cancer-associated pathways, indicating their key role in CRC pathogenesis. No significant DYRK mutations were identified, suggesting that DYRK expression variation in normal vs. tumor samples is likely linked to epigenetic regulation. The expression of DYRK1A and DYRK3 expression correlated with immune-infiltrating cells in the tumor microenvironment and was upregulated in MSI subtypes, pointing to their potential role as biomarkers for immunotherapy. This comprehensive bioinformatics analysis will set directions for future biological studies to further exploit the molecular basis of these findings and explore the potential of DYRK1A modulation as a novel targeted therapy for CRC.
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spelling pubmed-90258632022-04-23 A Bioinformatics Evaluation of the Role of Dual-Specificity Tyrosine-Regulated Kinases in Colorectal Cancer Laham, Amina Jamal El-Awady, Raafat Lebrun, Jean-Jacques Ayad, Maha Saber Cancers (Basel) Article SIMPLE SUMMARY: The dual-specificity tyrosine-regulated kinase (DYRK) family has been implicated in various diseases, including cancer. However, its role in colorectal cancer has not been elucidated. In this research, we used publicly available web-based tools to investigate DYRKs status in colorectal cancer. Our results showed that among DYRKs, only DYRK1A was upregulated significantly in late tumor stages, and it is associated with poor prognosis for colorectal cancer patients. These finding comprehensively characterized DYRK1A as a potential new therapeutic approach in CRC, especially in late tumor stages. ABSTRACT: Colorectal cancer (CRC) is the third most common cancer worldwide and has an increasing incidence in younger populations. The dual-specificity tyrosine-regulated kinase (DYRK) family has been implicated in various diseases, including cancer. However, the role and contribution of the distinct family members in regulating CRC tumorigenesis has not been addressed yet. Herein, we used publicly available CRC patient datasets (TCGA RNA sequence) and several bioinformatics webtools to perform in silico analysis (GTEx, GENT2, GEPIA2, cBioPortal, GSCALite, TIMER2, and UALCAN). We aimed to investigate the DYRK family member expression pattern, prognostic value, and oncological roles in CRC. This study shed light on the role of distinct DYRK family members in CRC and their potential outcome predictive value. Based on mRNA level, DYRK1A is upregulated in late tumor stages, with lymph node and distant metastasis. All DYRKs were found to be implicated in cancer-associated pathways, indicating their key role in CRC pathogenesis. No significant DYRK mutations were identified, suggesting that DYRK expression variation in normal vs. tumor samples is likely linked to epigenetic regulation. The expression of DYRK1A and DYRK3 expression correlated with immune-infiltrating cells in the tumor microenvironment and was upregulated in MSI subtypes, pointing to their potential role as biomarkers for immunotherapy. This comprehensive bioinformatics analysis will set directions for future biological studies to further exploit the molecular basis of these findings and explore the potential of DYRK1A modulation as a novel targeted therapy for CRC. MDPI 2022-04-18 /pmc/articles/PMC9025863/ /pubmed/35454940 http://dx.doi.org/10.3390/cancers14082034 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Laham, Amina Jamal
El-Awady, Raafat
Lebrun, Jean-Jacques
Ayad, Maha Saber
A Bioinformatics Evaluation of the Role of Dual-Specificity Tyrosine-Regulated Kinases in Colorectal Cancer
title A Bioinformatics Evaluation of the Role of Dual-Specificity Tyrosine-Regulated Kinases in Colorectal Cancer
title_full A Bioinformatics Evaluation of the Role of Dual-Specificity Tyrosine-Regulated Kinases in Colorectal Cancer
title_fullStr A Bioinformatics Evaluation of the Role of Dual-Specificity Tyrosine-Regulated Kinases in Colorectal Cancer
title_full_unstemmed A Bioinformatics Evaluation of the Role of Dual-Specificity Tyrosine-Regulated Kinases in Colorectal Cancer
title_short A Bioinformatics Evaluation of the Role of Dual-Specificity Tyrosine-Regulated Kinases in Colorectal Cancer
title_sort bioinformatics evaluation of the role of dual-specificity tyrosine-regulated kinases in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025863/
https://www.ncbi.nlm.nih.gov/pubmed/35454940
http://dx.doi.org/10.3390/cancers14082034
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