Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas
Epigenetics is involved in tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that the DNA methylation profiling may predict the clinical behavior of metastatic CRCs (mCRCs). The global methylation profile of two human mCRC subgroups with s...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/1/158 |
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| author | Valentina Condelli Giovanni Calice Alessandra Cassano Michele Basso Maria Grazia Rodriquenz Angela Zupa Francesca Maddalena Fabiana Crispo Michele Pietrafesa Michele Aieta Alessandro Sgambato Giampaolo Tortora Pietro Zoppoli Matteo Landriscina |
| author_facet | Valentina Condelli Giovanni Calice Alessandra Cassano Michele Basso Maria Grazia Rodriquenz Angela Zupa Francesca Maddalena Fabiana Crispo Michele Pietrafesa Michele Aieta Alessandro Sgambato Giampaolo Tortora Pietro Zoppoli Matteo Landriscina |
| author_sort | Valentina Condelli |
| collection | DOAJ |
| description | Epigenetics is involved in tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that the DNA methylation profiling may predict the clinical behavior of metastatic CRCs (mCRCs). The global methylation profile of two human mCRC subgroups with significantly different outcome was analyzed and compared with gene expression and methylation data from The Cancer Genome Atlas COlon ADenocarcinoma (TCGA COAD) and the NCBI GENE expression Omnibus repository (GEO) GSE48684 mCRCs datasets to identify a prognostic signature of functionally methylated genes. A novel epigenetic signature of eight hypermethylated genes was characterized that was able to identify mCRCs with poor prognosis, which had a CpG-island methylator phenotype (CIMP)-high and microsatellite instability (MSI)-like phenotype. Interestingly, methylation events were enriched in genes located on the q-arm of chromosomes 13 and 20, two chromosomal regions with gain/loss alterations associated with adenoma-to-carcinoma progression. Finally, the expression of the eight-genes signature and MSI-enriching genes was confirmed in oxaliplatin- and irinotecan-resistant CRC cell lines. These data reveal that the hypermethylation of specific genes may provide prognostic information that is able to identify a subgroup of mCRCs with poor prognosis. |
| first_indexed | 2024-03-10T13:27:55Z |
| format | Article |
| id | doaj.art-4e8c7b192e1b495ba1e4c7a35076fe0f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T13:27:55Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4e8c7b192e1b495ba1e4c7a35076fe0f2023-11-21T08:30:51ZengMDPI AGCancers2072-66942021-01-0113115810.3390/cancers13010158Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal CarcinomasValentina Condelli0Giovanni Calice1Alessandra Cassano2Michele Basso3Maria Grazia Rodriquenz4Angela Zupa5Francesca Maddalena6Fabiana Crispo7Michele Pietrafesa8Michele Aieta9Alessandro Sgambato10Giampaolo Tortora11Pietro Zoppoli12Matteo Landriscina13Laboratory of Preclinical and Translational Research, Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Potenza, ItalyLaboratory of Preclinical and Translational Research, Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Potenza, ItalyMedical Oncology Unit, Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, ItalyMedical Oncology Unit, Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, ItalyMedical Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Potenza, ItalyPathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Potenza, ItalyLaboratory of Preclinical and Translational Research, Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Potenza, ItalyLaboratory of Preclinical and Translational Research, Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Potenza, ItalyLaboratory of Preclinical and Translational Research, Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Potenza, ItalyMedical Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Potenza, ItalyLaboratory of Preclinical and Translational Research, Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Potenza, ItalyMedical Oncology Unit, Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, ItalyLaboratory of Preclinical and Translational Research, Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Potenza, ItalyLaboratory of Preclinical and Translational Research, Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Potenza, ItalyEpigenetics is involved in tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that the DNA methylation profiling may predict the clinical behavior of metastatic CRCs (mCRCs). The global methylation profile of two human mCRC subgroups with significantly different outcome was analyzed and compared with gene expression and methylation data from The Cancer Genome Atlas COlon ADenocarcinoma (TCGA COAD) and the NCBI GENE expression Omnibus repository (GEO) GSE48684 mCRCs datasets to identify a prognostic signature of functionally methylated genes. A novel epigenetic signature of eight hypermethylated genes was characterized that was able to identify mCRCs with poor prognosis, which had a CpG-island methylator phenotype (CIMP)-high and microsatellite instability (MSI)-like phenotype. Interestingly, methylation events were enriched in genes located on the q-arm of chromosomes 13 and 20, two chromosomal regions with gain/loss alterations associated with adenoma-to-carcinoma progression. Finally, the expression of the eight-genes signature and MSI-enriching genes was confirmed in oxaliplatin- and irinotecan-resistant CRC cell lines. These data reveal that the hypermethylation of specific genes may provide prognostic information that is able to identify a subgroup of mCRCs with poor prognosis.https://www.mdpi.com/2072-6694/13/1/158promoter methylationcolorectal carcinomagene signatureprognosisMSI-like signatureCIMP status |
| spellingShingle | Valentina Condelli Giovanni Calice Alessandra Cassano Michele Basso Maria Grazia Rodriquenz Angela Zupa Francesca Maddalena Fabiana Crispo Michele Pietrafesa Michele Aieta Alessandro Sgambato Giampaolo Tortora Pietro Zoppoli Matteo Landriscina Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas Cancers promoter methylation colorectal carcinoma gene signature prognosis MSI-like signature CIMP status |
| title | Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas |
| title_full | Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas |
| title_fullStr | Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas |
| title_full_unstemmed | Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas |
| title_short | Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas |
| title_sort | novel epigenetic eight gene signature predictive of poor prognosis and msi like phenotype in human metastatic colorectal carcinomas |
| topic | promoter methylation colorectal carcinoma gene signature prognosis MSI-like signature CIMP status |
| url | https://www.mdpi.com/2072-6694/13/1/158 |
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