Background:
Triple-negative breast cancer (TNBC) is associated with a poor prognosis.
Sphingosine-1-phosphate (S1P), a potent
sphingolipid metabolite, has been implicated in many processes that are important for
breast cancer (BC). S1P signaling regulates
tumorigenesis, and response to
chemotherapy and
immunotherapy by affecting the trafficking, differentiation or effector function of
tumor-infiltrating immune cells (TIICs). Objective: In this study, using bioinformatics tools and publicly available databases, we have analyzed the prognostic value of S1P metabolizing genes and their correlation with TIICs in BC patients. Methods: The expression of S1P metabolizing genes and receptors was evaluated by the UALCAN
cancer database. The correlation between
mRNA expression of S1P metabolizing genes and receptors and survival outcome of
breast cancer patients was analyzed by the Kaplan-Meier plotter database. The association between the gene expression and infiltration of immune cells in the
tumors was analyzed by "
Tumor-Infiltrating Immune Estimation Resource (TIMER). In silico
protein expression analysis was done using the Human
Protein Atlas" database. Results: TNBC patients with lower expression of
S1P phosphatase 1 (SGPP1) or
lipid phosphate phosphatase 3 (PLPP3) have much shorter relapse-free survival than the patients with a higher expression of these genes. SGPP1 and PLPP3 expression show a strong positive correlation with
tumor-infiltrating dendritic cells (DCs), CD4+ and CD8+ T cells, neutrophils, and macrophages in the TNBC subtypes. In addition,
S1P receptor 4 (S1PR4), an
S1P receptor exhibit a strong positive correlation with DCs, CD4+ and CD8+ T cells and neutrophils in TNBC. We, therefore, conclude that low expression of SGPP1 and PLPP3 may hinder the recruitment of immune cells to the
tumor environment, resulting in the blockage of
cancer cell clearance and a subsequent poor prognosis.