Urinary Measurement of Epigenetic DNA Modifications and 8-oxodG as Possible Noninvasive Markers of Colon Cancer Evolution
The active DNA demethylation mechanism involves 5-methylcytosine (5-mCyt) enzymatic oxidation with the subsequent formation of 5-hydroxymethylcytosine (5-hmCyt), which can be further oxidized to 5-formylcytosine (5-fCyt) and 5-carboxylcytosine (5-caCyt). The products of active DNA demethylation are...
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2022-11-01
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author | Aleksandra Skalska-Bugala Agnieszka Siomek-Gorecka Zbigniew Banaszkiewicz Ryszard Olinski Rafal Rozalski |
author_facet | Aleksandra Skalska-Bugala Agnieszka Siomek-Gorecka Zbigniew Banaszkiewicz Ryszard Olinski Rafal Rozalski |
author_sort | Aleksandra Skalska-Bugala |
collection | DOAJ |
description | The active DNA demethylation mechanism involves 5-methylcytosine (5-mCyt) enzymatic oxidation with the subsequent formation of 5-hydroxymethylcytosine (5-hmCyt), which can be further oxidized to 5-formylcytosine (5-fCyt) and 5-carboxylcytosine (5-caCyt). The products of active DNA demethylation are released into the bloodstream and eventually also appear in urine. We used online two-dimensional ultraperformance liquid chromatography with tandem mass spectrometry (2D-UPLC-MS/MS) to compare DNA methylation marks and 8-oxo-2′-deoxyguanosine (8-oxodG) in colorectal cancer and pre-cancerous condition in urine. The study included four groups of subjects: healthy controls, patients with inflammatory bowel disease (IBD), persons with adenomatous polyps (AD), and individuals with colorectal cancer (CRC). We have found that the level of 5-fCyt in urine was significantly lower for CRC and polyp groups than in the control group. The level of 5-hmCyt was significantly higher only in the CRC group compared to the control (2.3 vs. 2.1 nmol/mmol creatinine). Interestingly, we have found highly statistically significant correlation of 5-hydroxymethyluracil with 5-hydroxymethylcytosine, 5-(hydroxymethyl)-2′-deoxycytidine, 5-(hydroxymethyl)-2′-deoxyuridine, and 5-methyl-2′-deoxycytidine in the CRC patients’ group. |
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spelling | doaj.art-3ef46366f39142a08bf533af0fdc28b12023-11-24T08:34:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221382610.3390/ijms232213826Urinary Measurement of Epigenetic DNA Modifications and 8-oxodG as Possible Noninvasive Markers of Colon Cancer EvolutionAleksandra Skalska-Bugala0Agnieszka Siomek-Gorecka1Zbigniew Banaszkiewicz2Ryszard Olinski3Rafal Rozalski4Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, PolandDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, PolandDepartment of Surgery, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-168 Bydgoszcz, PolandDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, PolandDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, PolandThe active DNA demethylation mechanism involves 5-methylcytosine (5-mCyt) enzymatic oxidation with the subsequent formation of 5-hydroxymethylcytosine (5-hmCyt), which can be further oxidized to 5-formylcytosine (5-fCyt) and 5-carboxylcytosine (5-caCyt). The products of active DNA demethylation are released into the bloodstream and eventually also appear in urine. We used online two-dimensional ultraperformance liquid chromatography with tandem mass spectrometry (2D-UPLC-MS/MS) to compare DNA methylation marks and 8-oxo-2′-deoxyguanosine (8-oxodG) in colorectal cancer and pre-cancerous condition in urine. The study included four groups of subjects: healthy controls, patients with inflammatory bowel disease (IBD), persons with adenomatous polyps (AD), and individuals with colorectal cancer (CRC). We have found that the level of 5-fCyt in urine was significantly lower for CRC and polyp groups than in the control group. The level of 5-hmCyt was significantly higher only in the CRC group compared to the control (2.3 vs. 2.1 nmol/mmol creatinine). Interestingly, we have found highly statistically significant correlation of 5-hydroxymethyluracil with 5-hydroxymethylcytosine, 5-(hydroxymethyl)-2′-deoxycytidine, 5-(hydroxymethyl)-2′-deoxyuridine, and 5-methyl-2′-deoxycytidine in the CRC patients’ group.https://www.mdpi.com/1422-0067/23/22/13826DNA demethylationcolon cancerinflammatory bowel diseaseadenomaDNA epigenetic modification2D-UPLC-MS/MS |
spellingShingle | Aleksandra Skalska-Bugala Agnieszka Siomek-Gorecka Zbigniew Banaszkiewicz Ryszard Olinski Rafal Rozalski Urinary Measurement of Epigenetic DNA Modifications and 8-oxodG as Possible Noninvasive Markers of Colon Cancer Evolution International Journal of Molecular Sciences DNA demethylation colon cancer inflammatory bowel disease adenoma DNA epigenetic modification 2D-UPLC-MS/MS |
title | Urinary Measurement of Epigenetic DNA Modifications and 8-oxodG as Possible Noninvasive Markers of Colon Cancer Evolution |
title_full | Urinary Measurement of Epigenetic DNA Modifications and 8-oxodG as Possible Noninvasive Markers of Colon Cancer Evolution |
title_fullStr | Urinary Measurement of Epigenetic DNA Modifications and 8-oxodG as Possible Noninvasive Markers of Colon Cancer Evolution |
title_full_unstemmed | Urinary Measurement of Epigenetic DNA Modifications and 8-oxodG as Possible Noninvasive Markers of Colon Cancer Evolution |
title_short | Urinary Measurement of Epigenetic DNA Modifications and 8-oxodG as Possible Noninvasive Markers of Colon Cancer Evolution |
title_sort | urinary measurement of epigenetic dna modifications and 8 oxodg as possible noninvasive markers of colon cancer evolution |
topic | DNA demethylation colon cancer inflammatory bowel disease adenoma DNA epigenetic modification 2D-UPLC-MS/MS |
url | https://www.mdpi.com/1422-0067/23/22/13826 |
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