Abstract P3-10-01: Mir-150 expression is associated with immune cell infiltration and immune response in breast cancer
Authors: Masanori Oshi, Shipra Gandhi, Rongrong Wu, Li Yan, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe
Journal: Cancer Research (2022)

Abstract MicroRNA (miRNA) are known as a key player in tumor growth, and is shown to epigenetically regulate a large number of protein-coding genes, including tumor-related genes. MiR-150, a hematopoietic cell-specific miRNA, has been suggested to have various effects on cell proliferation, differentiation, apoptosis, migration, and invasion. However, there has been no study that investigated the role of miR-150 in the tumor microenvironment (TME) of breast cancer patients. We studied the clinical relevance of miR-150 expression by performing in silico analyses of 1961 breast cancer patients using multiple independent large cohorts. We found that miR-150 expression was strongly correlated with immune-related gene set scores, Allograft rejection, IL6/JAK/STAT3 signaling, Interferon (IFN)-γ response, Inflammatory response, IL2/STAT5 signaling, and complement, in Hallmark collection of gene set variation analyses consistently in both METABRIC and TCGA cohorts (all spearman’s rank correlation coefficient (r) &amp;gt; 0.50, all p &amp;lt; 0.01). MiR-150 expression was also strongly correlated with cytolytic activity (CYT) score in both cohorts (r = 0.824 and 0.786, respectively, both p &amp;lt; 0.01). Furthermore, miR-150 expression was significantly correlated with infiltrating fraction of CD8+ T cells (r = 0.799 and 0.525, respectively), CD4+ memory T cells (r = 0.759 and 0.656, respectively), dendritic cells (r = 0.735 and 0.696, respectively), and B cells (r = 0.759 and 0.576, respectively), as well as mRNA expression of major immune checkpoint molecules, including PD-1, CTLA4, IDO1, TIGIT, BTLA, and LAG3, in both cohorts (all r &amp;gt; 0.50, and all p &amp;lt; 0.01). MiR-150 expression in triple negative breast cancer (TNBC) was the highest when compared to other subtypes (both p &amp;lt; 0.001). A high miR-150 was significantly associated with high Nottingham grade (both p &amp;lt; 0.001). MiR-150 high tumor enriched not only immune-related gene sets but also apoptosis, KRAS signaling up, MTORC1, and p53 pathway by gene set enrichment analysis in both cohorts. A high miR-150 was significantly associated with better overall survival (OS) in both cohorts (p &amp;lt; 0.001 and p = 0.030, respectively). Subgroup analysis revealed that a high miR-150 was associated with better OS in ER-positive/HER2-negative breast cancer in both cohorts (p = 0.002 and 0.044, respectively), and in TNBC in the METABRIC cohort (p = 0.006). In conclusion, miR-150 expression is associated with immune cell infiltration and immune response, as well as with better survival in breast cancer patients. Citation Format: Masanori Oshi, Shipra Gandhi, Rongrong Wu, Li Yan, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe. Mir-150 expression is associated with immune cell infiltration and immune response in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-10-01.