Abstract P4-07-09: Differential expression of microRNAs (miRNAs) in HER2 negative breast cancer (BC)

Abstract

Abstract Background: MiRNAs are non-coding single-stranded RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Compared to mRNA signatures, miRNAs have better and stronger biomarker properties with 20 times more power in biomarker studies as compared to mRNAs (when comparing 20,000 mRNAs to ~ 1,000 miRNAs). Global downregulation of miRNAs has emerged as a common theme in human breast tumors and has been shown to contribute to oncogenesis Hormone receptor (HR) status is one of the most important factors influencing BC outcome. Several data indicate the extensive alterations in miRNAs regulation upon estrogen pathway and suggest the utility of considering miRNAs expression in the understanding the development of cancer disease, invasiveness, metastasis and treatment failure. Our aim was to identify differential expression miRNAs in HER2 negative BC. We previously reported a set of miRNAs deregulated in HR+/HER2- BC vs. Triple negative BC (TNBC). In this work we have validate these differences in a new cohort of BC patients. Methods: Total RNA was extracted samples extracted from primary breast cancer FFPE tissue. MicroRNAs expression was analyzed by RT-qPCR using TaqMan Arrays from Applied Biosystems. Normalization was performed using de DCt method with two housekeeping miRNAs identified previously identified using NorMean. MicroRNA expression values in each group were compared by the Mann Whitney test. Results: 121 patients with early HER2 negative BC were included in the present study. All patients showed absence of nodal involvement at the time of diagnosis. The median age at diagnosis was 56 years, 89 cases (74%) had positive estrogen receptor and 53 cases (44%) grade 3. miR-20a, miR-19a, miR-106a, miR-18a and miR-135b expression were significantly higher in TNBC samples, whereas miR-190b, miR-375, miR-449a, miR-342, miR-149, miR-193b, miR-214, miR-30a*and miR-30e* were significantly more expressed in ER+/HER2- samples. No significant differences were found in miR-139-5p expression between both groups. Conclusions: We have validated fourteen miRNAs that are differentially expressed between ER+/HER2- and TNBC breast cancer subtypes. Altered expression of miRNAs could be a potential therapeutic tool and promising biomarker in personalized treatment. Citation Format: Pascual T, Gámez-Pozo A, Camara-Jurado M, Manso LM, Pérez-Campos A, Trilla L, Fresno-Vara JA, Ciruelos EM. Differential expression of microRNAs (miRNAs) in HER2 negative breast cancer (BC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-07-09.