The Expression And Clinical Significance Of MiR-1258、miR-124 And Their Target Genes In Human Breast Cancer

Purpose: To investigate the expression of mi R-1258, mir-124 and their target genes changes in breast cancer. Try to determine whether they were involved in the development and progression of breast cancer.Methods:(1) MiR-1258 and HPSE expressions were analyzed in normal, benign and malignant breast tissues and metastatistic lymph nodes. Futhermore, their serum levels were evaluated in healthy women and in patients with benign and malignant breast disease. We analyzed the associations between their expressions and clinical features of patients.(2) MiR-124 expressions were analyzed in TNBC tissues and serum samples. Immunohistochemical stains for AR and E-cadherin were also performed in TNBC tissues. We analyzed the associations between their expressions and clinical features of patients.Results:(1) MiR-1258 was down-regulated and HPSE was up- regulated in breast cancer. They were significantly inversely correlated(P < 0.05). Statistically, reduced miR-1258 expression and elevated HPSE expression were associated with the lymph node status, high clinical stages, short overall survival and short relapse-free survival(P < 0.05). In frozen fresh tissue samples, the miR-1258 levels in breast cancer with lymph node metastasis were significantly lower than that of breast cancer without lymph node metastasis and benign disease(BD)(P < 0.05). In contrast, the HPSE levels in breast cancer with lymph node metastasis were the highest. In serums, the miR-1258 levels in metastatic breast cancer(M1) were lower than that of primary breast cancer(M0) and BD(P < 0.05). However, serum HPSE levels of M1 patients were significantly higher than that of M0 patients and BD patients(P < 0.05). In serums, reduced miR-1258 expression was associated with the lymph node status(P < 0.05), and elevated HPSE expression was associated with the lymph node status and high clinical stages(P < 0.05).(2) MiR-124 were down-regulated in tissues and serums of TNBC patients. MiR-124 expression was associated with tumor grade and E-cadherin expression(P < 0.05), but it was not associated with AR expression(P > 0.05). AR expression was associated with tumor grade and menopausal status(P < 0.05), and E-cadherin expression was associated with lymph node status(P < 0.05). A multivariate analysis demonstrated that tumor size, tumor grade, lymph node status and E-cadherin were of prognostic significance for disease-free survival and overall survival(P < 0.05). Compared to AR-positive patients, AR-negative patients showed significantly poorer outcomes with respect to the disease-free survival(P < 0.05) and overall survival(P < 0.05). E-cadherin-negative patients experienced shorter disease-free survival(P < 0.05) and poorer overall survival(P < 0.05) than did E-cadherin-positive patients. An AR-positive and E-cadherin-negative expression profile was associated with recurrence or metastasis(P < 0.05). Moreover, as the expression of nuclear AR increased, less E-cadherin staining was observed in TNBC samples. However, there is no relationship between miR-124 expression and patients survival.Conclusions:(1) MiR-1258 may play an important role in breast cancer development and progression through HPSE control. They might be potential prognostic biomarkers for breast cancer.(2) MiR-124 may play a tumor suppressor role in the development of TNBC and influence E-cadherin expression. AR and E-cadherin expression could be useful prognostic markers for classifying subgroups of TNBC.