Abstract PS19-24: Low expression MicroRNA-195 enriched the cell cycle and cell proliferation gene sets and is associated with advanced grades and worse overall survival of ER positive breast cancer patients

Abstract

Abstract Background: MicroRNA-195 (miR-195) exerts the tumor suppressive functions in various cancers, including breast cancer, by targeting and inhibiting the expressions of the cell cycle and cell proliferation associated genes. In this study, we hypothesized that miR-195 low expressing tumors associate with high proliferative characteristics and poor survival. Material and Methods: We obtained the clinicopathological data and survival information of breast cancer patients from two large publicly available databases; The Cancer Genome Atlas (TCGA) and The Molecular Taxonomy of Breast Cancer International Consortium (METARBRIC). Total of 755 and 1287 patients’ data were obtained from TCGA and METABRIC 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. 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-. Conclusion: 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. Citation Format: Yoshihisa Tokumaru, Masanori Oshi, Eriko Katsuta, Nobuhisa Matsuhashi, Manabu Futamura, Kazuhiro Yoshida, Kazuaki Takabe. Low expression MicroRNA-195 enriched the cell cycle and cell proliferation gene sets and is associated with advanced grades and worse overall survival of ER positive breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-24.