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

doi:10.18502/ijhoscr.v17i3.13303

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

Int J Hematol Oncol Stem Cell Res. 2023 Jul 1;17(3):133-144. doi: 10.18502/ijhoscr.v17i3.13303.

Authors

Sahar Khojastehpour¹, Farshad Foroughi^{2

3}, Nematollah Gheibi³, Zahra Mohammadi¹, Mohammad Hossein Ahmadi⁴, Neda Nasirian⁵, Amirhosein Maali^{6

7}, Mehdi Azad⁴

Affiliations

¹ Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran.
² Department of Immunology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
³ Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran.
⁴ Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
⁵ Department of Pathology, Qazvin University of Medical Sciences, Qazvin, Iran.
⁶ Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
⁷ Department of Medical Biotechnology, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

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.

Keywords: Breast cancer; Epigenetics; Gene expression; Methylation.