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Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression

Colorectal cancer (CRC) is a major cause of cancer mortality. Early diagnosis is relevant for its prevention and treatment. Since DNA methylation alterations are early events in tumourigenesis and can be detected in cell-free DNA, they represent promising biomarkers for early CRC diagnosis through n...

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Autores principales: Vega-Benedetti, Ana Florencia, Loi, Eleonora, Moi, Loredana, Orrù, Sandra, Ziranu, Pina, Pretta, Andrea, Lai, Eleonora, Puzzoni, Marco, Ciccone, Letizia, Casadei-Gardini, Andrea, Cabras, Francesco, Fortunato, Federica, Restivo, Angelo, Zorcolo, Luigi, Scartozzi, Mario, Zavattari, Patrizia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349989/
https://www.ncbi.nlm.nih.gov/pubmed/32599859
http://dx.doi.org/10.3390/ijms21124494
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author Vega-Benedetti, Ana Florencia
Loi, Eleonora
Moi, Loredana
Orrù, Sandra
Ziranu, Pina
Pretta, Andrea
Lai, Eleonora
Puzzoni, Marco
Ciccone, Letizia
Casadei-Gardini, Andrea
Cabras, Francesco
Fortunato, Federica
Restivo, Angelo
Zorcolo, Luigi
Scartozzi, Mario
Zavattari, Patrizia
author_facet Vega-Benedetti, Ana Florencia
Loi, Eleonora
Moi, Loredana
Orrù, Sandra
Ziranu, Pina
Pretta, Andrea
Lai, Eleonora
Puzzoni, Marco
Ciccone, Letizia
Casadei-Gardini, Andrea
Cabras, Francesco
Fortunato, Federica
Restivo, Angelo
Zorcolo, Luigi
Scartozzi, Mario
Zavattari, Patrizia
author_sort Vega-Benedetti, Ana Florencia
collection PubMed
description Colorectal cancer (CRC) is a major cause of cancer mortality. Early diagnosis is relevant for its prevention and treatment. Since DNA methylation alterations are early events in tumourigenesis and can be detected in cell-free DNA, they represent promising biomarkers for early CRC diagnosis through non-invasive methods. In our previous work, we identified 74 early altered CpG islands (CGIs) associated with genes involved in cell cross-talking and cell signalling pathways. The aim of this work was to test whether methylation-based biomarkers could be detected in non-invasive matrices. Our results confirmed methylation alterations of GRIA4 and VIPR2 in CRC tissues, using MethyLight, as well as in stool samples, using a much more sensitive technique as droplet digital PCR. Furthermore, we analysed expression levels of selected genes whose promoter CGIs were hypermethylated in CRC, detecting downregulation at mRNA and protein levels in CRC tissue for GRIA4, VIPR2, SPOCK1 and SLC6A3. Most of these genes were already lowly expressed in colon normal tissues supporting the idea that cancer DNA methylation targets genes already barely expressed in the matched normal tissues. Our study suggests GRIA4 and VIPR2 as biomarkers for early CRC diagnosis using stool samples and confirms downregulation of genes hypermethylated in CRC.
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spelling pubmed-73499892020-07-15 Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression Vega-Benedetti, Ana Florencia Loi, Eleonora Moi, Loredana Orrù, Sandra Ziranu, Pina Pretta, Andrea Lai, Eleonora Puzzoni, Marco Ciccone, Letizia Casadei-Gardini, Andrea Cabras, Francesco Fortunato, Federica Restivo, Angelo Zorcolo, Luigi Scartozzi, Mario Zavattari, Patrizia Int J Mol Sci Article Colorectal cancer (CRC) is a major cause of cancer mortality. Early diagnosis is relevant for its prevention and treatment. Since DNA methylation alterations are early events in tumourigenesis and can be detected in cell-free DNA, they represent promising biomarkers for early CRC diagnosis through non-invasive methods. In our previous work, we identified 74 early altered CpG islands (CGIs) associated with genes involved in cell cross-talking and cell signalling pathways. The aim of this work was to test whether methylation-based biomarkers could be detected in non-invasive matrices. Our results confirmed methylation alterations of GRIA4 and VIPR2 in CRC tissues, using MethyLight, as well as in stool samples, using a much more sensitive technique as droplet digital PCR. Furthermore, we analysed expression levels of selected genes whose promoter CGIs were hypermethylated in CRC, detecting downregulation at mRNA and protein levels in CRC tissue for GRIA4, VIPR2, SPOCK1 and SLC6A3. Most of these genes were already lowly expressed in colon normal tissues supporting the idea that cancer DNA methylation targets genes already barely expressed in the matched normal tissues. Our study suggests GRIA4 and VIPR2 as biomarkers for early CRC diagnosis using stool samples and confirms downregulation of genes hypermethylated in CRC. MDPI 2020-06-24 /pmc/articles/PMC7349989/ /pubmed/32599859 http://dx.doi.org/10.3390/ijms21124494 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vega-Benedetti, Ana Florencia
Loi, Eleonora
Moi, Loredana
Orrù, Sandra
Ziranu, Pina
Pretta, Andrea
Lai, Eleonora
Puzzoni, Marco
Ciccone, Letizia
Casadei-Gardini, Andrea
Cabras, Francesco
Fortunato, Federica
Restivo, Angelo
Zorcolo, Luigi
Scartozzi, Mario
Zavattari, Patrizia
Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression
title Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression
title_full Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression
title_fullStr Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression
title_full_unstemmed Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression
title_short Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression
title_sort colorectal cancer early detection in stool samples tracing cpg islands methylation alterations affecting gene expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349989/
https://www.ncbi.nlm.nih.gov/pubmed/32599859
http://dx.doi.org/10.3390/ijms21124494
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