Abstract P5-10-02: High serum levels of miR-19a are associated with poor outcome in metastatic inflammatory breast cancer

Abstract

Abstract Background: Increased expression of miR-19a plays an important role in tumor progression by regulating angiogenesis and apoptosis. As miRs can be a valuable diagnostic and prognostic serum biomarker, we assessed if high serum levels of miR-19a were associated with the shorter overall survival (OS) of patients with metastatic inflammatory breast cancer (MIBC) and metastatic non-inflammatory breast cancer (MNIBC). Methods: We analyzed 27 MNIBC (10 HER2 normal [HER2−] and 17 HER2 amplified [HER2+]), 37 MIBC (18 HER2− and 19 HER2+) patients, and 30 healthy donors (HDs). Patients' sera were collected before starting a new line of treatment. MiR-19a levels were measured in patients' sera and cell lines (MCF-7, SKBR3, MA-231, KPL-4, SUM-149) by qRT-PCR to assess differences in expression levels between IBC and non-IBC. MiR-192 and U6 snRNA were used to normalize miR-19a expression levels in serum and cell lines, respectively. Fold-changes in expression of miR-19a were calculated using the 2−DCt method. Mann-Whitney U test, ROC curve analysis, Kaplan-Meier, and Student's t-test were used for statistical analysis. Results: Median levels of miR-19a were higher in sera of both MNIBC and MIBC patients than in HDs (p = .001, p < 001, respectively). Median serum level of miR-19a was higher in MIBC than in MNIBC (p = .013). ROC curve analysis revealed that miR-19a could differentiate MNIBC from MIBC (AUC = 0.683; p = 0.013). With a cutoff value of 1.62 set by ROC, the sensitivity, specificity and positive predictive value (PPV) were 56.7%, 85.2%, and 84.0%, respectively. The triple receptor negative (TN) IBC cell line SUM-149 had the highest level of miR-19a and it was higher than the non-IBC: MDA-231 (TN; p = .031); SKBR3 (HER2+; p = .021); and MCF-7 (ER/PR+; p = .003). KPL-4 (IBC, HER2+) had the second highest miR-19a levels after SUM-149. MIBC patients had a shorter median OS than MNIBC patients (18.8 vs 27.8 months; p = .041; range, 0.7–40.3 months; median follow-up 19.5 months). MIBC patients with HER2− tumor (n = 11) and high serum levels of miR-19a (>1.62) had a shorter median OS than MNIBC patients with HER2− tumors (n = 9) and low serum level of miR-19a (<1.62) (16.15 vs 33.45 months; p = .025). There was no difference in the OS between HER2+ MIBC patients with high miR-19a (> 1.62) and HER2+ MNIBC patients with low miR-19a (<1.62). Discussion: In this pilot study, miR-19a may be a potential biomarker for inflammatory breast cancer, as significantly higher miR-19a levels were present in the sera of MIBC compared with MNIBC as well as in IBC compared with non-IBC cell lines. Furthermore, miR-19a may be predictive of OS, as HER2− MIBC patients with high serum levels of miR-19a had shorter OS than HER2− MNIBC patients with low serum levels of miR-19a. Our data suggest that high expression of miR-19a: is a feature of IBC tumor cells; can be detected in the serum; may favor tumor progression and predict poor outcome of HER2− MNIBC patient. A larger cohort of patients is required to confirm these observations and examine predictive potential. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-02.