LAUSR

The routine screening for breast cancer relies primarily on imaging techniques such as mammography and ultrasonography, but it is often not sensitive enough for early detection and requires complementary approaches. Recent studies suggest that microRNAs (miRNAs) could be used as biomarkers for breast cancer due to its relative stability in archived formalin-fixed tissues as well as in bodily fluids. However, the identity of unique miRNAs that could discriminate proliferative and malignant states of the disease has remained elusive. Since TGFβ-induced epithelial-mesenchymal transition (EMT) represents a critical step during tumor progression and intravasation, studying the cancer cell at the mesenchymal state and its precursor could help to identify these critical diagnostic biomarkers. To identify novel biomarkers for early detection, we performed miRNA gene expression profiling of an established basal-like breast cancer (BLBC) model system with and without disruption of TGFβ signaling. We have identified a panel of miRNAs, including miR-210-3p, that are highly expressed in the motile, mesenchymal stage, which could potentially be used as markers in liquid biopsies for early detection of invasive BLBC. Conversely, we also found some miRNAs, including miR-200c and miR-4417, highly expressed in the noninvasive, epithelial stage. Transient overexpression of miR-4417 in mesenchymal BLBC cells was able to suppress migration and mammosphere formation in vitro, suggesting that it could block progression of BLBC, a disease highly prevalent in young African-American women and lacks targeted therapy. Citation Format: Wong CK, Thiagalingam S. Identification of miRNA biomarkers for early diagnosis of basal-like breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-09.