Background and Aims:  Studies have demonstrated that miR-196a-5p expression is increased while miR-339-5p expression is decreased in breast cancer cells, so they may probably be the therapeutic targets or diagnostic markers for breast cancer. Therefore, this study was conducted to evaluate the application values of serum levels of miR-196a-5p and miR-339-5p in diagnosis of breast cancer. 
Methods: One hundred and seven patients with breast cancer (breast cancer group) treated during January 2016 to June 2017, along with 60 patients with benign breast disease (benign breast disease group) and 35 individuals undergoing healthy maintenance examination (healthy control group) during the same period were enrolled. The differences of serum levels of miR-196a-5p and miR-339-5p as well as the breast cancer-specific marker CA15-3 were compared among groups, and the diagnostic abilities of serum levels of the three indices were determined. In addition, the relationship between serum levels of miR-196a-5p and miR-339-5p in breast cancer patients as well as the associations of their levels with the clinicopathologic characteristics of breast cancer were also analyzed. 
Results: In healthy control group, benign breast disease group and breast cancer group, the serum levels of miR-196a-5p and miR-339-5p were successively increased and decreased respectively, and the differences between groups were all statistically significant (all P<0.01). the serum CA15-3 level in breast cancer group was significantly higher than that in benign breast disease group and healthy control group (both P<0.01), but the difference between the latter two groups showed no statistical significance (P>0.05). The diagnostic abilities for breast cancer of both serum miR-196a-5p and miR-339-5p levels were significantly superior to that of serum CA15-3 level (Z=2.543, P<0.05; Z=2.190, P<0.05), but the diagnostic abilities between miR-196a-5p and miR-339-5p showed no significant difference (P>0.05). The AUC of the combined detection of miR-196a-5p and miR-339-5p for diagnosis of breast cancer was 0.937, with the sensitivity and specificity 91.6% and 88.3% respectively, which was significantly superior to that of either lone detection (miR-196a-5p: Z=3.044, P<0.01; miR-339-5p: Z=3.020, P<0.01). There was a negative correlation between the preoperative serum expression levels of miR-196a-5p and miR-339-5p in breast cancer patients (r=–0.764, P<0.01), and serum miR-196a-5p level was decreased while the serum miR-339-5p level was increased significant after surgery compared with those before surgery in breast cancer patients (both P<0.01). The serum levels of both miR-196a-5p and miR-339-5p in breast cancer patients were significantly associated with tumor diameter, lymph node metastasis, and TNM stage (all P<0.01).
Conclusion: The determination of serum levels of miR-196a-5p and miR-339-5p has high diagnostic value and also has a potential monitoring value for breast cancer. Both diagnostic abilities of miR-196a-5p and miR-339-5p are superior to that of CA15-3, and their combined detection can further increase the diagnostic efficacy.