Expression of sphingosine-1-phosphate receptor 1 in patients with breast cancer and its influence on prognosis and immune infiltration

doi:10.3877/cma.j.issn.1674-6880.2025.02.004

Abstract

Abstract:

Objective

To investigate the influence of the expression level of sphingosine-1-phosphate receptor 1 (S1PR1) on the prognosis of breast cancer patients and its relationship with immune cell infiltration.

Methods

The GEPIA, TIMER, UALCAN, Kaplan-Meier Plotter,GENT2, cBioportal databases and the academic tool DAVID were used to analyze the influence of S1PR1 expression level on the prognosis of breast cancer patients, and the functional enrichment analysis on S1PR1-related genes was conducted. Meanwhile, the correlation between S1PR1 and infiltration abundance of six immune cells (B cells, CD8 ⁺T cells, CD4 ⁺T cells, macrophages,neutrophils and dendritic cells) in the overall breast cancer and different molecular subtypes[including basal-like, human epidermal growth factor receptor 2 (HER2) positive type and luminal breast cancers] was evaluated. The influence of infiltration abundance of various immune cells on the prognosis of breast cancer patients was analyzed by the Kaplan-Meier survival curve.

Results

The expression level of S1PR1 in breast cancer tissue was much lower than that in normal breast tissue, and there were statistically significant differences in S1PR1 expression levels among different clinical stages, lymph node metastasis status, molecular subtypes and tumor histological types (all P<0.05). Compared with normal breast tissue, the methylation level of S1PR1 promoter in primary breast cancer tissue was significantly higher (P < 0.05), and the methylation levels varied in different subtypes. Survival analysis indicated that the overall survival period and recurrence-free survival period of patients in the S1PR1 high-expression group were significantly better than those in the low-expression group (both P < 0.05). Gene function analysis indicated that the S1PR1-related genes were associated with immune deficiency.In the overall breast cancer samples, the expression level of S1PR1 was positively correlated with the infiltration abundance of CD8⁺T cells (r=0.461, P<0.001), CD4⁺T cells (r=0.391, P<0.001), macrophages (r=0.293, P<0.001), neutrophils (r=0.256, P<0.001) and dendritic cells(r=0.260, P<0.001). The survival curves of B cell high infiltration abundance in patients with overall breast cancer and HER2-positive breast cancer were much better than those of low infiltration abundance (P = 0.046, 0.017).

Conclusion

The expression of S1PR1 is associated with the prognosis of breast cancer patients and is involved in regulating the function of immune cells.

Key words: Sphingosine-1-phosphate receptor 1, Breast cancer, Immune infiltration, Prognosis, Bioinformatics

Letong Li, Jiaman Lin, Qiang Wang. Expression of sphingosine-1-phosphate receptor 1 in patients with breast cancer and its influence on prognosis and immune infiltration[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2025, 18(02): 105-114.

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References 33

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基因对	r值	P值
S1PR1-S1PR2	0.209	＜ 0.001
S1PR1-S1PR3	0.106	＜ 0.001
S1PR1-S1PR4	0.470	＜ 0.001
S1PR1-S1PR5	0.229	＜ 0.001
S1PR2-S1PR3	-0.228	＜ 0.001
S1PR2-S1PR4	0.524	＜ 0.001
S1PR2-S1PR5	0.327	＜ 0.001
S1PR3-S1PR4	-0.089	＜ 0.001
S1PR3-S1PR5	-0.072	0.024
S1PR4-S1PR5	0.286	＜ 0.001

基因对	r值	P值
S1PR1-S1PR2	0.209	＜ 0.001
S1PR1-S1PR3	0.106	＜ 0.001
S1PR1-S1PR4	0.470	＜ 0.001
S1PR1-S1PR5	0.229	＜ 0.001
S1PR2-S1PR3	-0.228	＜ 0.001
S1PR2-S1PR4	0.524	＜ 0.001
S1PR2-S1PR5	0.327	＜ 0.001
S1PR3-S1PR4	-0.089	＜ 0.001
S1PR3-S1PR5	-0.072	0.024
S1PR4-S1PR5	0.286	＜ 0.001

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