ABSTRACT: BACKGROUND:Sphingosine-1-phosphate receptor (S1PR1) is involved in vascular development, a key process in tumorigenesis. This study aimed to evaluate its roles in tumor development and prognosis. METHODS:S1PR1 expression levels were analyzed using TIMER and Oncomine database, and the prognostic significance of S1PR1 was assessed using PrognoScan and Kaplan-Meier plotter databases. The relationship between S1PR1 and tumor-infiltrated immune cells was analyzed using TIMER. RESULTS:S1PR1 expression was remarkably lower in breast and lung cancer tissues than in the corresponding normal tissues. Lower expression was related to poor overall survival and disease-free survival in breast invasive carcinoma (BRCA), lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC). A functional network analysis confirmed the function of S1PR1 in regulating vasculogenesis. In addition, S1PR1 levels were significantly negative with regard to the tumor purity of BRCA (r?=?-?0.508, P?= 1.76e-66), LUAD (r?=?-?0.353, P?= 6.05e-16), and LUSC (r?=?-?0.402, P?=?-?5.20e-20). Furthermore, S1PR1 levels were significantly positive with regard to infiltrating CD8+ (r?=?0.38, P?= 5.91e-35) and CD4+ T cells (r?=?0.335, P?= 1.03e-26), macrophages (r?=?0.219, P?= 3.67e-12), neutrophils (r?=?0.168, P?= 2.03e-7), and dendritic cells (DCs) (r?=?0.208, P?= 9.14e-11) in BRCA; S1PR1 levels were significantly positive with regard to CD8+ T cells (r?=?0.308, P?= 3.61e-12), macrophages (r?=?0.376, P?= 1.01e-17), neutrophils (r?=?0.246, P?= 4.15e-8), and DCs (r?=?0.207, P?= 4.16e-6) in LUAD; and positive with regard to B cells (r?=?0.356, P?= 1.57e-15), CD8+ (r?=?0.459, P?= 3.83e-26) and CD4+ T cells (r?=?0.338, P?= 3.98e-14), macrophages (r?=?0.566, P?= 2.61e-45), neutrophils (r?=?0.453, P?= 1.79e-25), and DCs (r?=?0.56, P?= 2.12e-40) in LUSC. CONCLUSIONS:S1PR1 levels are positively correlated with multiple immune markers in breast and lung cancer. These observed correlations between S1PR1 and the prognosis and immune cell infiltration provide a foundation for further research on its immunomodulatory role in cancer.
