Low expression of microRNA-195 is a poor prognostic marker for ER-positive breast cancer patients.

Abstract

e12576 Background: MicroRNA-195 (miR-195) is a tumor suppressive microRNA in breast cancer; however, its clinical relevance remains debatable because most data is either in\xa0vitro or from small cohort studies. In this study, we hypothesized that miR-195 low expressing tumors associate with high proliferative characteristics and poor survival. Methods: We obtained the clinical data and survival information of breast cancer patients from two large publicly available databases and one small cohort; The Cancer Genome Atlas (TCGA),The Molecular Taxonomy of Breast Cancer International Consortium (METARBRIC), and GSE45666. Total of 755, 1287, and 116 patients’ data were obtained from TCGA, METABRIC, and GSE45666 respectively. Survival analysis, Overall survival (OS) and Disease-free survival (DFS) was performed by comparing the high and low expression groups. CYT score, xCell, and other immunological factors were used to evaluate intratumoral immune cell composition. Also, gene set enrichment analysis (GSEA) was performed between miR-195 high and low expression groups. Results: The patients were divided into miR-195 high and low groups by utilizing median cutoff. At first, we confirmed that miR-195 expression was significantly lower in tumors compared to normal breast tissue in TCGA as well as GSE45666. Advanced grades were significantly associated with lower expression of miR-195 in ER positive/HER2 negative (ER+/HER2) subtype with both TCGA and METABRIC cohorts ( p< 0.001 and p< 0.001, respectively). On the contrary this was not consistent with other subtypes, HER2+ and triple negative (TN). Also, Low miR-195 expressing tumors demonstrated higher MKI67 expressions in ER+/HER2- subtype with TCGA ( p< 0.001). This was validated with METABRIC cohort ( p< 0.001). Furthermore, GSEA demonstrated that low miR-195 expressing tumors enriched the gene sets related with cell cycle or cell proliferation, such as MYC signaling, mTOR signaling, E2F signaling, G2M Checkpoint signaling and PI3K_Akt_mTOR signaling, compared with high miR-195 expressing tumors in ER+/HER2-. Conclusions: Low expression of miR-195 was associated with improved OS in ER positive breast cancer patients. Also, low miR-195 expressing tumors were found to associate with advanced grades as well as enriching the genes relating to cell proliferation and cell cycle, which may explain the poor survival of low miR-195 expressing patients in ER positive breast cancer.