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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/12/4494 |
| _version_ | 1797564255178850304 |
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| author | Ana Florencia Vega-Benedetti Eleonora Loi Loredana Moi Sandra Orrù Pina Ziranu Andrea Pretta Eleonora Lai Marco Puzzoni Letizia Ciccone Andrea Casadei-Gardini Francesco Cabras Federica Fortunato Angelo Restivo Luigi Zorcolo Mario Scartozzi Patrizia Zavattari |
| author_facet | Ana Florencia Vega-Benedetti Eleonora Loi Loredana Moi Sandra Orrù Pina Ziranu Andrea Pretta Eleonora Lai Marco Puzzoni Letizia Ciccone Andrea Casadei-Gardini Francesco Cabras Federica Fortunato Angelo Restivo Luigi Zorcolo Mario Scartozzi Patrizia Zavattari |
| author_sort | Ana Florencia Vega-Benedetti |
| collection | DOAJ |
| 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 <i>GRIA4</i> and <i>VIPR2</i> 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 <i>GRIA4</i> and <i>VIPR2</i> as biomarkers for early CRC diagnosis using stool samples and confirms downregulation of genes hypermethylated in CRC. |
| first_indexed | 2024-03-10T18:54:48Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:54:48Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e9dc42563597464c9ae8b5de0df1d3ca2023-11-20T04:51:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012112449410.3390/ijms21124494Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene ExpressionAna Florencia Vega-Benedetti0Eleonora Loi1Loredana Moi2Sandra Orrù3Pina Ziranu4Andrea Pretta5Eleonora Lai6Marco Puzzoni7Letizia Ciccone8Andrea Casadei-Gardini9Francesco Cabras10Federica Fortunato11Angelo Restivo12Luigi Zorcolo13Mario Scartozzi14Patrizia Zavattari15Department of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, 09042 Cagliari, ItalyDepartment of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, 09042 Cagliari, ItalyDepartment of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, 09042 Cagliari, ItalyDepartment of Pathology, “A. Businco” Oncologic Hospital, ASL Cagliari, 09121 Cagliari, ItalyDepartment of Medical Oncology, University Hospital of Cagliari, 09042 Cagliari, ItalyDepartment of Medical Oncology, University Hospital of Cagliari, 09042 Cagliari, ItalyDepartment of Medical Oncology, University Hospital of Cagliari, 09042 Cagliari, ItalyDepartment of Medical Oncology, University Hospital of Cagliari, 09042 Cagliari, ItalyBio-Rad Laboratories srl, Southern Europe, 20090 Milan, ItalyDivision of Oncology, Department of Oncology and Hematology, University Hospital of Modena, 41125 Modena, ItalyDepartment of Surgery, Colorectal Surgery Center, University of Cagliari, 09042 Cagliari, ItalyDepartment of Surgery, Colorectal Surgery Center, University of Cagliari, 09042 Cagliari, ItalyDepartment of Surgery, Colorectal Surgery Center, University of Cagliari, 09042 Cagliari, ItalyDepartment of Surgery, Colorectal Surgery Center, University of Cagliari, 09042 Cagliari, ItalyDepartment of Medical Oncology, University Hospital of Cagliari, 09042 Cagliari, ItalyDepartment of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, 09042 Cagliari, ItalyColorectal 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 <i>GRIA4</i> and <i>VIPR2</i> 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 <i>GRIA4</i> and <i>VIPR2</i> as biomarkers for early CRC diagnosis using stool samples and confirms downregulation of genes hypermethylated in CRC.https://www.mdpi.com/1422-0067/21/12/4494Colorectal cancer (CRC)CpG islandscancer methylation alterationsCRC early diagnosisbiomarkers<i>GRIA4</i> |
| spellingShingle | Ana Florencia Vega-Benedetti Eleonora Loi Loredana Moi Sandra Orrù Pina Ziranu Andrea Pretta Eleonora Lai Marco Puzzoni Letizia Ciccone Andrea Casadei-Gardini Francesco Cabras Federica Fortunato Angelo Restivo Luigi Zorcolo Mario Scartozzi Patrizia Zavattari Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression International Journal of Molecular Sciences Colorectal cancer (CRC) CpG islands cancer methylation alterations CRC early diagnosis biomarkers <i>GRIA4</i> |
| 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 | Colorectal cancer (CRC) CpG islands cancer methylation alterations CRC early diagnosis biomarkers <i>GRIA4</i> |
| url | https://www.mdpi.com/1422-0067/21/12/4494 |
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