Abstract PR5: Prognostic value of miRNAs in breast cancer: Molecular type and patient race

Abstract

Background: MicroRNAs (miRNAs) are a class of conserved, non-coding RNAs that are dysregulated in various cancers, including breast cancers. The potential of miRNAs to serve as biomarkers for breast cancer diagnosis and prognosis is being explored, but their clinical value based on race/ethnicity and molecular subtypes (luminal and triple negative breast cancers, TNBCs) has not been examined. Thus, we evaluated expression levels of a panel of miRNAs in luminal (A and B) breast cancers and TNBCs of African Americans (Blacks) and non-Hispanic Caucasians (Whites). We further evaluated the prognostic value of miRNAs based on molecular type of breast cancer and patient race. Methods: TaqMan® miRNA assays were used to quantify expression of miR-181a, miR181b, miR-21, miR-106a, miR-155, miR-210, miR-335, miR-206, and miR-126 in 105 breast cancers (luminal=51 and TNBCs=54) and their corresponding benign/normal tissues. Cancer tissuefrom 48 Blacks (luminal=23 and TNBCs=25) and 57 Whites (luminal=28 and TNBC=29) were analyzed. Fold change in the expression levels between tumor-normal pairs were determined using the 2-∆∆Ct method. A cutoff value for each miRNA was determined by utilizing the Cutoff Finder software application [PLoS ONE 7(12):e51862, 2012]. The cutoff values were used to categorize the tumors into two groups (High expression or positive and low expression or negative). The expression status of tumors was correlated with patient overall survival by univariate Kaplan-Meier analysis. Results: Since the survival probabilities of Blacks and Whites with TNBCs (log rank, p=0.899) were similar, TNBCs from both racial groups were pooled. Similarly, no survival differences were noted in patients of both racial groups with luminal breast cancers (log rank, p=0.178). Therefore, luminal cancers of Blacks and Whites were also pooled together to perform survival analyses based on miRNA expression levels. MiRNA expression profiling studies indicated that, in both the racial groups, miR-181a, miR-181b, miR-21, miR-106a, miR-155, and miR-210 were up-regulated in luminal cancers and TNBCs. In contrast, miR-335, miR-206, and miR-126 were down-regulated in both molecular types. When the prognostic value of miRNAs was evaluated in each molecular type separately, it was found that over-expression of miR-106a (p=0.037) and miR-210 (p=0.039) were associated with poor prognosis of TNBCs. However, none of the evaluated miRNAs were useful in assessing the prognosis of patients with luminal cancers. Conclusions: These findings suggest that increased expression of miR-106a and miR-210 were poor prognostic indicators of TNBCs collected from both Black and White patients. Additionally, our results suggest that in the evaluation of clinical utility of miRNAs molecular types of breast cancer should be considered. This study was funded in part by the National Cancer Institute of the National Institute of Health UAB/TU/MSM Partnership grant (U54 CA118948). This abstract is also presented as Poster C21. Citation Format: Balananda-Dhurjati Kumar Putcha, Trafina Jadhav, Shantel Hebert-Magee, Jeehyun Helen Bae, Andra R. Frost, Isam-Eldin Eltoum, Sejong Bae, Upender Manne. Prognostic value of miRNAs in breast cancer: Molecular type and patient race. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PR5. doi:10.1158/1538-7755.DISP13-PR5