The Association of Methylation Status and Expression Level of MyoD1 with DNMT1 Expression Level in Breast Cancer Patients.

Sahar Khojastehpour, Farshad Foroughi, Nematollah Gheibi, Zahra Mohammadi, Mohammad Hossein Ahmadi, Neda Nasirian, Amirhosein Maali, Mehdi Azad
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Abstract

Background: Breast cancer (BC) is the most common malignancy in women worldwide. The methylation status of MyoD1, a tumor suppressor gene, is enrolled in various cancers, i.e., BC. Various studies showed the impact of MyoD1 epigenetic dysregulation in BC. This study aimed to investigate the methylation status and expression level of MyoD1 in BC patients and its association with the expression of DNMT1. Materials and Methods: This case-control study was conducted on 30 cases (pathology-confirmed ductal carcinoma) and 18 controls (fibroadenoma and fibrocystic masses), referred to Velayat Hospital, Qazvin, Iran. The expression of the MyoD1 and DNMT1 and the promoter methylation of the MyoD1 were evaluated in tissue blocks of BC patient masses using qRT-PCR and MS-PCR assays, respectively. SPSS 24.0 was used to analyze the data. Results: The MyoD1 promoter is hypermethylated in BC patients compared to controls (p =0.001). The expression level of MyoD1 in BC patients was significantly reduced compared to controls (fold change =0.13, p =0.042). In addition, in BC patients, the reduced expression level of MyoD1 was significantly associated with methylation of the MyoD1 promoter (p =0.001). There is no significant difference between the expression level of DNMT1 in BC patients and controls (p =0.197). A significant association is found between the expression of DNMT1 and the methylation status of the MyoD1 promoter (p =0.038). Discussion: The expression level of MyoD1 is affected by the methylation status of the promoter of this gene. Moreover, the expression level and methylation status of MyoD1 are correlated with clinical parameters.

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癌症患者MyoD1甲基化状态和表达水平与DNMT1表达水平的相关性。
背景:癌症是全球女性最常见的恶性肿瘤。肿瘤抑制基因MyoD1的甲基化状态被纳入各种癌症,即BC。各种研究表明MyoD1表观遗传学失调对BC的影响。本研究旨在探讨BC患者MyoD1的甲基化状态和表达水平及其与DNMT1表达的关系。材料和方法:这项病例对照研究对30例(经病理证实的导管癌)和18例对照(纤维腺瘤和纤维囊性肿块)进行,这些病例被转诊至伊朗Qazvin Velayat医院。分别使用qRT-PCR和MS-PCR测定在BC患者肿块的组织块中评估MyoD1和DNMT1的表达以及MyoD1的启动子甲基化。采用SPSS 24.0软件对数据进行统计分析。结果:与对照组相比,BC患者的MyoD1启动子高度甲基化(p=0.001)。与对照组比较,BC患者MyoD1的表达水平显著降低(倍数变化=0.13,p=0.042)。此外,在BC患者中,MyoD1的表达水平降低与MyoD1启动子的甲基化显著相关(p=0.001)。不列颠哥伦比亚省患者和对照组的DNMT1表达水平没有显著差异(p=0.017)MyoD1受该基因启动子甲基化状态的影响。此外,MyoD1的表达水平和甲基化状态与临床参数相关。
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