Prognostic Value of MUC1 and its Correlation with Tumor-Infiltrating Immune Cells in Breast Cancer

Abstract Background: MUC1 is a transmembrane glycoprotein, aberrantly glycosylated and overexpressed in a variety of epithelial cancers, and plays a crucial role in cancer progression, especially in breast cancer. It is also an essential regulator for immune functionality, but the mechanisms whereby it effects immune infiltration in breast cancer remain uncertain. Methods: In this research, MUC1 expression was analyzed by the Oncomine and TIMER database. The association between MUC1 and prognosis was evaluated by Kaplan-Meier plotter database. The correlations of MUC1 with immune infiltration and immunological markers were assessed by TIMER database. Results: We found that MUC1 expression was significantly correlated with outcomes in multiple cancers, with the effect being particularly pronounced in breast cancer. Pathologically, elevated MUC1 expression was related with worse prognosis depending on intrinsic subtypes, ER status, patient stage, lymph node and TP53 mutation status in breast cancer. Specifically, low level of MUC1 seemed to be more favorable to luminal B patients with systemic treatment. MUC1 expression had significant negative correlations with infiltrating levels of CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, monocytes and dendritic cells (DCs) in breast cancer. Besides, MUC1 displayed strong regulations on macrophage polarization and diverse immunological gene markers. The patients with lower MUC1 and deeper immune infiltration predicted better prognosis. Conclusions: MUC1 is significantly associated with clinical prognosis and potentially plays an essential role in modulating cytotoxic T lymphocytes (CTLs), tumor associated macrophages (TAMs), natural killer cells (NK cells) and DCs in breast tumors. Collectively, MUC1 could be served as a valuable biomarker of predicting prognosis and immune infiltration for breast cancer patients.