Analysis Of Related Gene Methylation And Influential Factors In Sporadic Breast Cancer

IntroductionBreast cancer is women's most common malignancy, recent study suggests that epigenetic changes in sporadic breast cancer pathogenesis mechanism plays an important role. DNMT and HDAC are two important enzymes in epigenetic changes, and associate with gene methylation closely. Breast cancer susceptibility genes BRCA1 is closely related to breast cancer, gene mutation, promoter methylation and allelic loss of heterozygosity are common approach of BRCA1 gene expression silencing. In sporadic breast cancer, BRCA1 gene promoter methylation and BRCA1 gene deletions are more common.MethodsDNMT1, DNMT3a, DNMT3b and HDAC1, HDAC2 protein expression were detected in 292 cases of sporadic breast cancer and 44 cases of breast fibroadenoma tissues using immunohistochemistry (SP method) BRCA1 gene copy numbers of 100 cases of sporadic breast cancer and 19 cases of breast fibroadenoma were detected using fluorescence in situ hybridization(FISH). Then, the association of above results with clinical pathological features were analysed.ResultsThe expression levels of DNMT1, DNMT3a, DNMT3b and HDAC1, HDAC2 were not significantly different between breast cancer and fibroadenoma tissues. DNMT1 and HDAC2 expression levels in carcinoma with lymph node metastasis were significantly higher than those without metastasis (P=0.024,0.030); In different tumor type of breast cancer, HDAC2 expression were significantly different, with invasive ductal carcinoma having the highest positive rate (P= 0.007). In ERP-positive tissues, HDAC1, HDAC2 and DNMT3a expression levels were significantly higher than ERβ-negative tissues (P= 0.001,0.009,0.006); DNMT3b and BRCA1 protein expression showed significant positive correlation (P=0.020); DNMT3a expression of HER2-positive group weas significantly higher than HER2-negative group (P=0.033); The expression of HDAC2 showed significant positive correlation with HER2, p53, c-Myc (P= 0.007,0.028,0.002); In MRP-positive tissues, HDAC1 expression was significantly increased (P=0.002), and in BCRP-positive tissues, HDAC2 expression was significantly higher (P=0.041). In breast cancer tissues with BRCA1 promoter methylation, BRCA1 gene copy number was significantly lower than unmethylated group (P=0.008); BRCA1 gene copy number was significantly lower in breast cancer tissues with BRCA1 protein negative expression than the positive expression group (P =0.020).ConclusionThe high level of DNMT1, DNMT3a, DNMT3b and HDAC1, HDAC2 protein expression has a certain correlation with sporadic breast cancer development and drug resistance, and especially of HDAC2. In sporadic breast cancer, BRCA1 gene promoter methylation often accompanied by loss of BRCA1 gene copy.