Abstract P3-08-59: High expression microRNA-143 is associated with favorable tumor immune microenvironment and better survival of ER positive breast cancer patients

Abstract

Abstract Background: MicroRNA-143(miR-143) is known to function as the tumor suppressor in various cancers, including breast cancer. The tumor immune microenvironment such as the balance between the T helper cell type 1 (Th1) and Th2 is reported to associate with the survival of the breast cancer patients. In this study, we hypothesized that the miR-143 has favorable effect to the tumor immune microenvironment. Material and Methods: We obtained the clinicopathological data and survival information of 755 breast cancer patients from The Cancer Genome Atlas (TCGA) database. Survival analysis, Overall survival (OS) and Disease free survival (DFS) was conducted comparing the high and low expression groups. CYT score, CIBERSORT, and other immunological factors were used to evaluate intratumoral immune cell composition within estrogen receptor (ER) positive breast cancer patients. Also, gene set enrichment analysis (GSEA) was performed between miR-143 high and low expression groups within the ER positive group. Results: High expression of miR-143 was significantly associated with prolonged OS only in ER positive breast cancer patients (p=0.014). Expression of miR-143 was not associated with DFS, stage, TNM factors of breast cancer patients. Within ER positive patients, the result of CIBERSORT revealed that high expression of miR-143 was associated with higher percentage of macrophage M1 (p<0.03) and lower percentage of macrophage M2 (p<0.001). There was more Th1 cells in miR-143 high group (p<0.001) whereas Th2 cells were less (p<0.001). This result was strikingly echoed by GSEA, where miR-143 high significantly enriched the genes related to Th1 cells compared with that of Th2 cells. Regulatory T cell, Lymphocyte infiltration signature score, and T cell receptor diversity were higher in the patients with high miR-143 expression (p<0.03, p<0.001, and p<0.001 respectively). CYT score that reflect cytolytic activity was higher in the high miR-143 expression group (p<0.04). Conclusion: High expression of miR-143 was associated with improved OS in ER positive breast cancer patients. Also, miR-143 was found to associate with high Th1 and low Th2 cells as well as enriching the genes relating to Th1 cells, which may explain the favorable role of miR-143 in ER positive breast cancer. Citation Format: Yoshihisa Tokumaru, Masanori Oshi, Mariko Asaoka, Takashi Takeshita, Eriko Katsuta, Manabu Futamura, Kazuhiro Yoshida, Kazuaki Takabe. High expression microRNA-143 is associated with favorable tumor immune microenvironment and better survival of ER positive breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-59.