Interaction between Microsatellite Instability (MSI) and Tumor DNA Methylation in the Pathogenesis of Colorectal Carcinoma
In colorectal cancer (CRC), the role of microsatellite instability (MSI) is well known. In a genome-wide scale, for the first time, we explored whether differential methylation is associated with MSI. We analyzed 250 paired samples from 125 CRC patients (m = 72, f = 53) at different stages. Of them,...
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ftmdpi:oai:mdpi.com:/2072-6694/13/19/4956/ 2023-08-20T04:06:09+02:00 Interaction between Microsatellite Instability (MSI) and Tumor DNA Methylation in the Pathogenesis of Colorectal Carcinoma Farzana Jasmine Zahidul Haq Mohammed Kamal Maruf Raza Gustavo da Silva Katrina Gorospe Rupash Paul Patrick Strzempek Habibul Ahsan Muhammad G Kibriya 2021-10-01 application/pdf https://doi.org/10.3390/cancers13194956 EN eng Multidisciplinary Digital Publishing Institute Molecular Cancer Biology https://dx.doi.org/10.3390/cancers13194956 https://creativecommons.org/licenses/by/4.0/ Cancers; Volume 13; Issue 19; Pages: 4956 MSI colorectal cancer interaction CIMP MMR immune checkpoint inhibitor CTLA4 HAVCR2 Text 2021 ftmdpi https://doi.org/10.3390/cancers13194956 2023-08-01T02:51:36Z In colorectal cancer (CRC), the role of microsatellite instability (MSI) is well known. In a genome-wide scale, for the first time, we explored whether differential methylation is associated with MSI. We analyzed 250 paired samples from 125 CRC patients (m = 72, f = 53) at different stages. Of them, 101 had left-sided CRC, 30 had MSI, 34 had somatic mutation in KRAS proto-oncogene (KRAS), and 6 had B-Raf proto-oncogene (BRAF) exon 15p.V600E mutation. MSI was more frequent in right-sided tumors (54% vs. 17%, p = 0.003). Among the microsatellite stable (MSS) CRC, a paired comparison revealed 1641 differentially methylated loci (DML) covering 686 genes at FDR 0.001 with delta beta ≥ 20%. Similar analysis in MSI revealed 6209 DML covering 2316 genes. ANOVA model including interaction (Tumor*MSI) revealed 23,322 loci, where the delta beta was different among MSI and MSS patients. Our study shows an association between MSI and tumor DNA methylation in the pathogenesis of CRC. Given the interaction seen in this study, it may be worth considering the MSI status while looking for methylation markers in CRC. The study also indicates an opportunity for potential use of certain immune checkpoint inhibitors (CTLA4 and HAVCR2 inhibitors) in CRC with MSI. Text DML MDPI Open Access Publishing Cancers 13 19 4956 |
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MDPI Open Access Publishing |
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English |
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MSI colorectal cancer interaction CIMP MMR immune checkpoint inhibitor CTLA4 HAVCR2 |
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MSI colorectal cancer interaction CIMP MMR immune checkpoint inhibitor CTLA4 HAVCR2 Farzana Jasmine Zahidul Haq Mohammed Kamal Maruf Raza Gustavo da Silva Katrina Gorospe Rupash Paul Patrick Strzempek Habibul Ahsan Muhammad G Kibriya Interaction between Microsatellite Instability (MSI) and Tumor DNA Methylation in the Pathogenesis of Colorectal Carcinoma |
topic_facet |
MSI colorectal cancer interaction CIMP MMR immune checkpoint inhibitor CTLA4 HAVCR2 |
description |
In colorectal cancer (CRC), the role of microsatellite instability (MSI) is well known. In a genome-wide scale, for the first time, we explored whether differential methylation is associated with MSI. We analyzed 250 paired samples from 125 CRC patients (m = 72, f = 53) at different stages. Of them, 101 had left-sided CRC, 30 had MSI, 34 had somatic mutation in KRAS proto-oncogene (KRAS), and 6 had B-Raf proto-oncogene (BRAF) exon 15p.V600E mutation. MSI was more frequent in right-sided tumors (54% vs. 17%, p = 0.003). Among the microsatellite stable (MSS) CRC, a paired comparison revealed 1641 differentially methylated loci (DML) covering 686 genes at FDR 0.001 with delta beta ≥ 20%. Similar analysis in MSI revealed 6209 DML covering 2316 genes. ANOVA model including interaction (Tumor*MSI) revealed 23,322 loci, where the delta beta was different among MSI and MSS patients. Our study shows an association between MSI and tumor DNA methylation in the pathogenesis of CRC. Given the interaction seen in this study, it may be worth considering the MSI status while looking for methylation markers in CRC. The study also indicates an opportunity for potential use of certain immune checkpoint inhibitors (CTLA4 and HAVCR2 inhibitors) in CRC with MSI. |
format |
Text |
author |
Farzana Jasmine Zahidul Haq Mohammed Kamal Maruf Raza Gustavo da Silva Katrina Gorospe Rupash Paul Patrick Strzempek Habibul Ahsan Muhammad G Kibriya |
author_facet |
Farzana Jasmine Zahidul Haq Mohammed Kamal Maruf Raza Gustavo da Silva Katrina Gorospe Rupash Paul Patrick Strzempek Habibul Ahsan Muhammad G Kibriya |
author_sort |
Farzana Jasmine |
title |
Interaction between Microsatellite Instability (MSI) and Tumor DNA Methylation in the Pathogenesis of Colorectal Carcinoma |
title_short |
Interaction between Microsatellite Instability (MSI) and Tumor DNA Methylation in the Pathogenesis of Colorectal Carcinoma |
title_full |
Interaction between Microsatellite Instability (MSI) and Tumor DNA Methylation in the Pathogenesis of Colorectal Carcinoma |
title_fullStr |
Interaction between Microsatellite Instability (MSI) and Tumor DNA Methylation in the Pathogenesis of Colorectal Carcinoma |
title_full_unstemmed |
Interaction between Microsatellite Instability (MSI) and Tumor DNA Methylation in the Pathogenesis of Colorectal Carcinoma |
title_sort |
interaction between microsatellite instability (msi) and tumor dna methylation in the pathogenesis of colorectal carcinoma |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2021 |
url |
https://doi.org/10.3390/cancers13194956 |
genre |
DML |
genre_facet |
DML |
op_source |
Cancers; Volume 13; Issue 19; Pages: 4956 |
op_relation |
Molecular Cancer Biology https://dx.doi.org/10.3390/cancers13194956 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/cancers13194956 |
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Cancers |
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13 |
container_issue |
19 |
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4956 |
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1774717087942443008 |