| Objective: To investigate the relationship between the expression of microRNA-146a(miR-146a)and the clinical features and prognosis of early breast invasive ductal carcinoma(IDC)and to evaluate its diagnostic and prognostic value.Methods:(1)In situ hybridization(ISH)was used to detect the expression of miR-146 a in 289 cases of early IDC,meanwhile,The expression of ER,PR and HER-2 in some patients with pathological indexes were detected by immunohistochemistry(IHC),investigate the correlation of mi R-146 a expression with clinical pathological features and molecular subtypes,Kaplan-Meier method was used to calculate cumulative tumor-free survival time,log-rank test for median tumor-free survival time analysis,multi-factor analysis for prognosis of patients with early breast IDC.(2)The expression of miR-146 a was detected by quantitative real-time polymerase chain reaction(qRT-PCR)in 60 cases of early breast IDC Cancer and matched adjacent normal tissues.To compare the expression of miR-146 a in early breast IDC tissues and adjacent tissues with different molecular subtypes,and to verify the correlation between mi R-146 a expression and clinicopathological features.(3)30 cases of early breast IDC were enrolled.At the same time,30 healthy volunteers and 20 patients with breast fibroadenoma were selected as control group,and Serum samples were collected.The expression of miR-146 a in each group was quantified by qRT-PCR.The difference of mi R-146 a expression between the three groups was compared.The relationship between the expression of miR-146 a and clinicopathological features was analyzed,and Assessing the diagnostic efficacy of mi R-146 a in early breast IDC.Results:(1)(1)ISH was used to detect the expression of mi R-146 a in paraffin-embedded cancer tissue of 289 patients with early breast IDC.The positive expression rate of miR-146 a was 66.1%.The expression of mi R-146 a in early breast IDC was statistically significant in the difference of lymph node metastasis,recurrence and metastasis,ER,PR,and HER-2 status(P<0.05).The expression of mi R-146 a in early breast IDC was not statistically significant in the difference of groups in age at diagnosis,menstrual state,and mass size(P>0.05).(2)In the early 289 cases of early breast IDC patients,the difference of median tumor-free survival time was statistically significant between patients with positive miR-146 a expression and negative patients(P<0.05),Compared with patients with negative miR-146 a expression,patients with positive miR-146 a expression had longer median survival time and better prognosis.(3)we divided into four molecular subtypes of early breast IDC,The expression of mi R-146 a was different in the four groups,the difference is statistically significant difference(P<0.05).(4)In 106 patients with early breast IDC,the survival analysis results showed that median tumor-free survival time of patients with positive miR-146 a expression was longer than that of negative patients,The difference between the groups was statistically significant(P<0.05).(5)In 68 Luminal B type,mi R-146 a expression of survival analysis showed that there was no significant difference in median tumor-free survival time between the positive miR-146 a expression group and the negative miR-146 a expression group(P>0.05).(6)In 45 cases of HER2-enriched type of early breast IDC,miR-146 a expression of survival analysis showed that there was no significant difference in median tumor-free survival time between the positive miR-146 a expression group and the negative miR-146 a expression group(P>0.05).(7)In 70 cases of Basal-like type,The median tumor-free survival time in miR-146 a positive group was significantly higher than that in mi R-146 a negative group.the difference of median tumor-free survival time was statistically significant Significance(P<0.05).(8)Multivariate survival analysis showed that ER(P=0.049),radiotherapy(P=0.028)and miR-146a(P=0.041)were prognostic factors for early breast IDC.The negative expression of miR-146a(HR=1.876),ER negative(HR=1.909)and no radiotherapy(HR=1.688)were prognostic risk factors.(2)(1)The expression of miR-146 a was significantly decreased in early breast IDC cancer tissues.The relative expression levels of miR-146 a in 60 cases of early breast IDC and its adjacent normal tissues in this study were 1.494±1.341 and 2.127±1.881,respectively There was statistical significance(P<0.05).(2)Molecular subtypes were grouped and mi R-146 a expression of breast cancer tissues was decreased compared with adjacent normal tissues in HER2-enriched type,which was up-regulated in Basal-like type.(3)The expression of miR-146 a in lymph node metastasis in 60 cases of primary early breast IDC samples was significantly different(P<0.05).(3)(1)Data analysis of serum miR-146 a from the research showed that: compared with healthy normal volunteer group and breast fibroadenoma group,serum miR-146 a expression level was significantly upregulated in early breast IDC group(P<0.05),whereas there was no significant difference in patients between normal volunteer group and breast fibroadenoma group of serum miR-146 a expression level(P>0.05).(2)The expression of serum miR-146 a in patients in early breast IDC showed no significant difference in clinical pathological features such as age,ER,PR,HER-2,tumor size(P>0.05).high serum miR-146 a level were associated with Axillary lymph node metastases(P<0.05).(3)ROC curve analysis revealed that The area under the ROC curve of serum mi R-146 a in the diagnosis of early breast IDC(AUC)was 0.731(95% CI: 0.604-0.858),sensitivity: 93.50%,specificity: 44.40%,Accuracy: 79.70%).Serum miR-146 a has high diagnostic efficacy.Conclusion:(1)In primary early breast IDC tumor tissue samples,miR-146 a expression correlates with lymph node metastasis,recurrence and metastasis,and HER-2,The positive expression of miR-146 a suggested a good prognosis.(2)The expression of miR-146 a in different molecular subtypes of early breast IDC tissue is different,Compared to paracancerous normal tissue,miR-146 a expression is down-regulated in HER-2-enriched type and up-regulated in Basal-like type,suggesting that there may be differences in the biological behavior of different molecular subtypes of early breast IDC.(3)Differential expression of serum miR-146 a in patients with early breast IDC and healthy subjects,miR-146 a was significantly upregulated in serum of patients with early breast IDC,and serum miR-146 a was associated with lymph node metastasis.(4)miR-146 a plays a role of tumor suppressor in early breast IDC and has complex regulatory mechanisms,which is expected to become a candidate molecular biomarker for the diagnosis and prognosis of early breast IDC. |
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