Circulating miR-19a and miR-205 in serum may predict the sensitivity of luminal A subtype of breast cancer patients to neoadjuvant chemotherapy with epirubicin plus paclitaxel

Abstract

Background: The luminal A subtype of breast cancer has a good prognosis and is sensitive to endocrine therapy but is less sensitive to chemotherapy. It is necessary to identify biomarkers to predict chemosensitivity and avoid over-treatment. We hypothesized that miRNAs in the serum might be associated with chemosensitivity.

Methods: Sixty-eight breast cancer patients received neoadjuvant chemotherapy with epirubicin plus paclitaxel. The serum of the patients was collected before chemotherapy and stored at -80°C. The samples were classified into two groups in term of the chemosensitivity. We identified the differential expression patterns of miRNAs between the chemotherapy sensitive and resistant groups using microRNA profiling. Four miRNAs that were differentially expressed between the two groups were further validated in another 56 samples. We created a model fitting formula and a receiver operating characteristics (ROC) curve using logistic regression analysis to evaluate the prediction potency.

Results: We identified 8 miRNAs differentially expressed between the two groups: 6 miRNAs were up-regulated, and 2 miRNAs were down-regulated in the resistant group compared with the sensitive group. The expression of miR-19a and miR-205 were determined to have significant differences between the two groups (P<0.05). A predictive model of these two miRNAs was created by the logistic regression analysis. The probability of this model was 89.71%. Based on the ROC curve, the specificity was 75.00%, and the sensitivity was 81.25%.

Conclusions: The combination of miR-19a and miR-205 in the serum may predict the chemosensitivity of luminal A subtype of breast cancer to epirubicin plus paclitaxel neoadjuvant chemotherapy.

Figure 1. Differences in the microRNAs expression levels between the sensitive and resistant groups.

The expression level of serum miR-19a and miR-205 in luminal A breast cancer was examined by qRT-PCR. The relative levels of miR-19a and miR-205 normalized to its expression in sensitive group, respectively (set as 1). Mean± s.d. R: resistant, S: sensitive. *p<0.01.

Figure 2. The scatter diagram of circulating miR-19a, miR-205, miR-484 and miR-375 in 56 luminal A breast cancer patients.

Quantitative real-time PCR analysis of miR-19a, miR-205, miR-484 and miR-375 in resistant group (n = 24) and sensitive group (n = 32). Mean± s.d.

Figure 3. The predictive value of miR-19a and miR-205 expression regarding luminal A breast cancer patients' treatment responses.

A ROC curve analysis for miR-19a and miR-205 expression was performed to assess the luminal A breast cancer treatment response.