Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker
One challenge in colorectal cancer (CRC) is identifying novel biomarkers to be introduced in screening programs. The present study investigated the promoter methylation status of the SEPT9 gene in peripheral blood samples of subjects’ positive fecal occult blood test (FOBT). In order to add new insi...
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doaj-0a5f87e7066543178930314166f530792020-11-25T01:13:46ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-12-011612284862849710.3390/ijms161226113ijms161226113Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer BiomarkerGloria Ravegnini0Juan Manuel Zolezzi Moraga1Francesca Maffei2Muriel Musti3Corrado Zenesini4Vittorio Simeon5Giulia Sammarini6Davide Festi7Patrizia Hrelia8Sabrina Angelini9Department of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, 40126 Bologna, ItalyDepartment for Life Quality Studies, University of Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyUnit of Epidemiology, Health Promotion and Risk Communication, Department of Public Health, Bologna Local Health Authority, Via del Seminario1, 40068 San lazzaro di Savena, ItalyUnit of Epidemiology and Biostatistics, IRCCS, ISNB, Via Altura 3, 40139 Bologna, ItalyLaboratory of Pre-Clinical and Translational Research Reference Cancer Center of Basilicata, Scientific Institute of Hospitalization and Treatment, Rionero in Vulture, 85028 Potenza, ItalyDepartment of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, 40126 Bologna, ItalyDepartment of Clinical Medicine, University of Bologna, Via Massarenti 9, 40138 Bologna, ItalyDepartment of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, 40126 Bologna, ItalyOne challenge in colorectal cancer (CRC) is identifying novel biomarkers to be introduced in screening programs. The present study investigated the promoter methylation status of the SEPT9 gene in peripheral blood samples of subjects’ positive fecal occult blood test (FOBT). In order to add new insights, we investigated the association between SEPT9 promoter methylation and micronuclei frequency, and polymorphisms in the folate-related pathway genes. SEPT9 promoter methylation, micronuclei frequency, and genotypes were evaluated on 74 individuals’ FOBT positive. Individuals were subjected to a colonoscopy that provided written informed consent for study participation. SEPT9 promoter methylation status was significantly lower in the CRC group than controls (p = 0.0006). In contrast, the CaCo2 cell-line, analyzed as a tissue specific model of colon adenocarcinoma, showed a significantly higher percentage of SEPT9 promoter methylation compared to the CRC group (p < 0.0001). Linear regression analysis showed an inverse correlation between micronuclei frequency and the decrease in the methylation levels of SEPT9 promoter region among CRC patients (β = −0.926, p = 0.0001). With regard to genotype analysis, we showed the involvement of the DHFR polymorphism (rs70991108) in SEPT9 promoter methylation level in CRC patients only. In particular, the presence of at least one 19 bp del allele significantly correlates with decreased SEPT9 promoter methylation, compared to the 19 bp ins/ins genotype (p = 0.007). While remaining aware of the strengths and limitations of the study, this represents the first evidence of a novel approach for the early detection of CRC, using SEPT9 promoter methylation, micronuclei frequency and genotypes, with the potential to improve CRC risk assessment.http://www.mdpi.com/1422-0067/16/12/26113SEPT9 methylationmicronucleigenetic polymorphismscolorectal cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gloria Ravegnini Juan Manuel Zolezzi Moraga Francesca Maffei Muriel Musti Corrado Zenesini Vittorio Simeon Giulia Sammarini Davide Festi Patrizia Hrelia Sabrina Angelini |
spellingShingle |
Gloria Ravegnini Juan Manuel Zolezzi Moraga Francesca Maffei Muriel Musti Corrado Zenesini Vittorio Simeon Giulia Sammarini Davide Festi Patrizia Hrelia Sabrina Angelini Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker International Journal of Molecular Sciences SEPT9 methylation micronuclei genetic polymorphisms colorectal cancer |
author_facet |
Gloria Ravegnini Juan Manuel Zolezzi Moraga Francesca Maffei Muriel Musti Corrado Zenesini Vittorio Simeon Giulia Sammarini Davide Festi Patrizia Hrelia Sabrina Angelini |
author_sort |
Gloria Ravegnini |
title |
Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker |
title_short |
Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker |
title_full |
Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker |
title_fullStr |
Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker |
title_full_unstemmed |
Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker |
title_sort |
simultaneous analysis of sept9 promoter methylation status, micronuclei frequency, and folate-related gene polymorphisms: the potential for a novel blood-based colorectal cancer biomarker |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2015-12-01 |
description |
One challenge in colorectal cancer (CRC) is identifying novel biomarkers to be introduced in screening programs. The present study investigated the promoter methylation status of the SEPT9 gene in peripheral blood samples of subjects’ positive fecal occult blood test (FOBT). In order to add new insights, we investigated the association between SEPT9 promoter methylation and micronuclei frequency, and polymorphisms in the folate-related pathway genes. SEPT9 promoter methylation, micronuclei frequency, and genotypes were evaluated on 74 individuals’ FOBT positive. Individuals were subjected to a colonoscopy that provided written informed consent for study participation. SEPT9 promoter methylation status was significantly lower in the CRC group than controls (p = 0.0006). In contrast, the CaCo2 cell-line, analyzed as a tissue specific model of colon adenocarcinoma, showed a significantly higher percentage of SEPT9 promoter methylation compared to the CRC group (p < 0.0001). Linear regression analysis showed an inverse correlation between micronuclei frequency and the decrease in the methylation levels of SEPT9 promoter region among CRC patients (β = −0.926, p = 0.0001). With regard to genotype analysis, we showed the involvement of the DHFR polymorphism (rs70991108) in SEPT9 promoter methylation level in CRC patients only. In particular, the presence of at least one 19 bp del allele significantly correlates with decreased SEPT9 promoter methylation, compared to the 19 bp ins/ins genotype (p = 0.007). While remaining aware of the strengths and limitations of the study, this represents the first evidence of a novel approach for the early detection of CRC, using SEPT9 promoter methylation, micronuclei frequency and genotypes, with the potential to improve CRC risk assessment. |
topic |
SEPT9 methylation micronuclei genetic polymorphisms colorectal cancer |
url |
http://www.mdpi.com/1422-0067/16/12/26113 |
work_keys_str_mv |
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