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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ftdoajarticles:oai:doaj.org/article:b70b09f5c81c484d95adc3dba6a76697 2023-10-01T03:55:39+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 2021-10-01T00:00:00Z https://doi.org/10.3390/cancers13194956 https://doaj.org/article/b70b09f5c81c484d95adc3dba6a76697 EN eng MDPI AG https://www.mdpi.com/2072-6694/13/19/4956 https://doaj.org/toc/2072-6694 doi:10.3390/cancers13194956 2072-6694 https://doaj.org/article/b70b09f5c81c484d95adc3dba6a76697 Cancers, Vol 13, Iss 4956, p 4956 (2021) MSI colorectal cancer interaction CIMP MMR immune checkpoint inhibitor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 article 2021 ftdoajarticles https://doi.org/10.3390/cancers13194956 2023-09-03T00:44:15Z 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. Article in Journal/Newspaper DML Directory of Open Access Journals: DOAJ Articles Cancers 13 19 4956 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
MSI colorectal cancer interaction CIMP MMR immune checkpoint inhibitor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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MSI colorectal cancer interaction CIMP MMR immune checkpoint inhibitor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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 |
Article in Journal/Newspaper |
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 |
MDPI AG |
publishDate |
2021 |
url |
https://doi.org/10.3390/cancers13194956 https://doaj.org/article/b70b09f5c81c484d95adc3dba6a76697 |
genre |
DML |
genre_facet |
DML |
op_source |
Cancers, Vol 13, Iss 4956, p 4956 (2021) |
op_relation |
https://www.mdpi.com/2072-6694/13/19/4956 https://doaj.org/toc/2072-6694 doi:10.3390/cancers13194956 2072-6694 https://doaj.org/article/b70b09f5c81c484d95adc3dba6a76697 |
op_doi |
https://doi.org/10.3390/cancers13194956 |
container_title |
Cancers |
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13 |
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19 |
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4956 |
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