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

Gloria Ravegnini²  Juan Manuel Zolezzi Moraga²  Francesca Maffei¹  Muriel Musti³  Corrado Zenesini⁴  Vittorio Simeon⁵  Giulia Sammarini²  Davide Festi⁶  Patrizia Hrelia²  Sabrina Angelini²  William Chi-shing Cho⁷ 

[1] Department for Life Quality Studies, University of Bologna, Corso d’Augusto 237, 47921 Rimini, Italy;Department of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, 40126 Bologna, Italy;Unit of Epidemiology, Health Promotion and Risk Communication, Department of Public Health, Bologna Local Health Authority, Via del Seminario1, 40068 San lazzaro di Savena, Italy;Unit of Epidemiology and Biostatistics, IRCCS, ISNB, Via Altura 3, 40139 Bologna, Italy;Laboratory of Pre-Clinical and Translational Research Reference Cancer Center of Basilicata, Scientific Institute of Hospitalization and Treatment, Rionero in Vulture, 85028 Potenza, Italy;Department of Clinical Medicine, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy;;Department of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, 40126 Bologna, Italy

关键词: SEPT9 methylation;    micronuclei;    genetic polymorphisms;    colorectal cancer;   

DOI  :  10.3390/ijms161226113

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.