RESUMO
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.
RESUMO
AIMS: The hypermethylation of CpG islands in the promoter of tumor-suppressor genes (TSGs) leads to silencing the transcription of tumor suppressors, which lead to the development of cancer. The hypermethylation of CXX1 and CDH1 genes, as TSGs, plays an essential role in the development of various types of cancer, i.e., colorectal and gastric cancer. This study aims at evaluating the expression level of CXX1 and CDH1 genes and the methylation status of CXX1 CpG island's promoter in breast cancer (BC). MATERIALS AND METHODS: In this study, the expression level of the CXX1 and CDH1 genes and the promoter methylation status of the CXX1 gene were evaluated in 30 paraffin-embedded tissue blocks of malignant BC and 18 benign breast lesions, using quantitative reverse transcription-PCR and methylation-specific (MS)-PCR assays, respectively. RESULTS: The CXX1 gene was downregulated in the malignant tissues due to the hypermethylation of the CpG islands in the promoter, compared to the control group (P = 0.031). The downregulation of CDH1 gene expression was observed in the patient group compared to control, but this reduction was not statistically significant. The results show that the risk of BC is increased with aging (P < 0.001). Furthermore, the benign breast lesions (controls) had more mobility in comparison with the malignant breast tumors (P < 0.001). In the malignant samples, the size of the mass was larger than control's mass samples (P = 0.006). CONCLUSIONS: In the pathophysiological state of BC, the aberrant DNA hypermethylation in CpG island of CXX1 promoter is responsible for the reduction of its expression level in BC patients.