Abstract A04: Identification of differentially expressed micro-RNAs in African American women with quadruple-negative breast cancer
Authors: Angajala Anusha , Hughley Raymond , Shweta Tripathi , Dean-Colomb Windy , Tan Ming , Yates Clayton 
Published: February 2019

Purpose: Recently, we have demonstrated that triple-negative breast tumors (TNBC) that lack the expression of androgen receptor are quadruple-negative tumors (QNBC) and have increased aggressiveness. Additionally, we determined that this is due to a unique gene signature in the QNBC subtype. However, whether this gene signature is associated with a unique miRNA expression and differential in African American (AA) women compared to Caucasian (CA) women has not been determined. Therefore, the purpose of this study is to determine the miRNA expression in presence or absence of androgen receptor in both African American and Caucasian QNBC patients

Methods: miRNA level 3 sequencing files were originally downloaded on June 1, 2016, from TCGA for 925 breast cancer patients. The miRNA sequence files(RPKM) and gene expression files (FPKM UQ) were obtained for normal and tumor samples for these patients. Median value of AR FPKM UQ was used as the cutoff and divided patient group as AR(+ve/-ve). Log2 fold change values were calculated by comparing AR-negative and AR-positive patients. P-value was calculated using two-tail t-test. MiRbase and MiRsystem were used for miRNA clustering and pathway analysis. GSE19783 (mRNA, miRNA data) was also obtained and was used as validating dataset.

Results: Out of 925 patients, 101 patients have TNBC. Among TNBC patients, 107 are QNBC and 8 patients are AR-positive TNBC. Reads per million for 1046 miRNAs were considered for this study.40 miRNAs showed differential expression in QNBC (p-value &lt;0.05). All BC patients were organized based on race (CA/AA), stage (I/II/III, IV), and subtype (luminal, Her2 type, TNBC). Expression of these 40 oncogenic miRNAs is checked in these groups. We have found that 6 miRNAs highly correlated to patient survival, race, and subtype (Hsa-mir-181a-2, Hsa-mir-500a, Hsa-mir-9.3, Hsa-let-7d, Hsa-mir-203b, Hsa-mir-584, Hsa-mir-210, Hsa-mir-455, Hsa-mir-190b); 8 miRNA correlated to Stage I, race, and subtype (Hsa-mir-210, Hsa-mir-196, Hsa-mir-937, Hsa-mir-375, Hsa-mir-150, Hsa-mir-17, Hsa-mir-181d,Hsa-mir-9.3, Hsa-mir-412, Hsa-mir-135b, Hsa-mir-500a); 22 miRNAs highly correlated to race and subtype (Hsa-mir-577, Hsa-mir-934, Hsa-mir-18a, Hsa-mir-19a, Hsa-mir-20a, Hsa-mir-92a-1, Hsa-mir-19b-1, Hsa-mir-30a, Hsa-mir-19b-2, Hsa-mir-92a-2, Hsa-mir-106a, Hsa-mir-130a, Hsa-mir-181b-2, Hsa-mir-425, Hsa-mir-1468, Hsa-mir-217, Hsa-mir-6510, Hsa-mir-3607, Hsa-mir-628, Hsa-mir-9-2, Hsa-mir-9-1, Hsa-mir-452); and 3 miRNAs correlated to stage, survival, race, and subtype (Hsa-mir-500a, Hsa-mir-9-3, Hsa-mir-210).

Discussion/Conclusion: Standard treatment of breast cancer relies on reliable assessment by IHC analysis of ER, PR, and HER2. Our results suggest that the heterogeneity of TNBC is at least partially associated with the presence or absence of AR expression, suggesting that QNBC should be considered as a clinically relevant breast cancer subtype. IHC analysis of AR appears to be a practical assay to determine the most aggressive TNBC subtypes and identifies tumors that could benefit from available targeted therapies. miRNA isoform or novel miRNA needs to be discovered to further investigate the gene regulation for QNBC patients.

Acknowledgment: MSM/TU/UAB Comprehensive Cancer Center Partnership [NCI]: U54 CA11862.

Citation Format: Anusha Angajala, Raymond Hughley, Tripathi Shweta, Windy Dean-Colomb, Ming Tan, Clayton Yates. Identification of differentially expressed micro-RNAs in African American women with quadruple-negative breast cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A04.