Abstract:

Objective To explore the relationship between the expression of DNA methylation and microRNA-328（miR-328）as well as the association of miR-328 with clinicopathological features and prognosis of invasive breast cancer.Methods In a retrospective analysis，the miR-328 expression levels of 1090 cases of invasive breast cancer tissues and 104 cases of adjacent tissues from TCGA breast cancer microarray from January 1998 to December 2013 were collected. The methylation rates of miR-328 CpG promoter region（cg16421621 and cg04650403）and correlation of methylation rates of CpG sites with the level of miR-328 were analyzed from 775 cases of invasive breast cancer tissues and 98 cases of adjacent tissues obtained from TCGA_BRCA_hMethyl450 microarray data. From the clinical_data_dictionary UCSC Genome Browser chip data，854 cases with complete clinicopathological data and follow-up data of breast cancer specimens were included for the analysis of the relationship of miR-328 with clinicopathological features and prognosis. The prognostic factors affecting the prognosis were exploited using Cox multivariate analysis. Results From January 1998 to December 2013, TCGA database of 1194 cases of breast cancer and adjacent tissues with expression of miR-328 showed that the miR-328 level of 1090 cases of invasive breast cancer tissues was 5.224 ±1.155，lower than 6.246±0.923 of 104 cases of adjacent tissues，and the difference was statistically significant（P＜0.01）. The methylation rates of cg16421621 and cg04650403 in the promoter region of miR-328 were（0.415±0.201）% and（0.193±0.068）% in 775 cases of invasive breast cancer，higher than（0.407±0.222）% and （0.094±0.079）% of 98 cases of adjacent tissues（P＜0.01）. The expression of miR-328 in invasive breast cancer was negatively correlated with the methylation rate of CG sites（cg16421621 and cg04650403）in the promoter region（r=-0.127，P=0.005）. In 854 cases of invasive breast cancer patients with complete clinical data, the expression level of miR328 was related to lymph node metastasis and tumor size（P＜0.05）. In miR-328 low expression group，the median overall survival（OS）was 7.25 years，lower than 8.75 years of high expression group（P＜0.01）. Cox multivariate analysis showed that age，lymph node metastasis and miR328 expression were independent factors influencing OS（P＜0.05），and the risk of high expression group was lower than that of low expression group（P＜0.01）.Conclusion MiR-328 expression is regulated by methylation of the promoter region of its gene in invasive breast cancer. MiR-328 is associated with clinicopathological features of invasive breast cancer，and can be used as a risk factor influencing the prognosis of invasive breast cancer.