Overexpression of sphingosine kinase 1 is predictive of poor prognosis in human breast cancer

Abstract

Sphingosine kinase 1 (SPHK1) is a bioactive lipid mediator that has been identified as a biomarker in various cancers and is considered to play an important role in tumor progression. In the present study, the expression level of SPHK1 was examined in breast cancer clinical specimens, and its association with patient survival was investigated to clarify the clinical significance of SPHK1 in breast cancer. SPHK1 mRNA expression was increased in breast cancer tissues compared with that in matched adjacent breast tissues in 19 of 32 paired tissue specimens (59.4%). Immunohistochemical analysis of 122 breast cancer cases revealed that the expression levels of SPHK1 were upregulated in 64 tumor tissues (52.5%), and increased expression levels of the protein were significantly associated with the presence of lymph node metastasis (P=0.0016), number of positive lymph nodes (P=0.0268) and presence of distant metastasis (P=0.0097). Increased SPHK1 protein expression was also associated with human epidermal growth factor receptor 2 status (P=0.0100), initial symptoms (P=0.0025) and tumor location (P=0.0457). Patients with increased SPHK1 protein expression had shorter overall survival and disease-free survival times compared with patients with lower SPHK1. Univariate and multivariate analyses indicated that high SPHK1 expression may be a poor prognostic factor. These results indicated that SPHK1 may perform an important role in breast cancer and may be a predictive factor in patients with breast cancer.

Predictive Value of Sphingosine Kinase 1 Expression in Papillary Thyroid Carcinoma

“…Guan et al (31) reported that sphingosine kinase 1 expression in thyroid cancer is up-regulated and associated with expression of proliferating cell nuclear antigen and showed that silencing of sphingosine kinase 1 suppresses proliferation of thyroid cancer cells. Other studies have shown that increased sphingosine kinase 1 expression is associated with lymph node metastasis and distant metastasis of breast cancer (36). These findings are consistent with our data showing that high sphingosine kinase 1 expression is associated with aggressive oncogenic behavior including tumor multiplicity, extrathyroidal extension, and lymph node metastasis.…”

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

“…SphK is increased in breast cancer [46,47] and is activated by cytokines, resulting in increases in intracellular S1P [48]. SphK-induced S1P accumulation suppresses apoptosis [49].…”

Sphingosine Kinase 1 Regulates the Survival of Breast Cancer Stem Cells and Non-stem Breast Cancer Cells by Suppression of STAT1

“…Overexpression of SPHK1 is associated with tumorigenic cell behavior that involves promoting cell growth, migration, and inhibiting apoptosis [24][25][26][38][39][40][41]44]. Recent studies also indicated that SPHK1-S1P may play a role in regulating CSCs populations in breast cancer models.…”

“…Several studies have indicated that increased SPHK1 activity promotes cancer cell growth, metastasis, and inhibits apoptosis [24][25][26][38][39][40][41]. Indeed, high expression of SPHK1 in tumors is associated with worse prognosis and overall outcomes in breast cancer patients [41][42][43][44][45][46][47][48]. In addition, overexpression of SPHK1 in breast cancer cells was reported to increase breast CSCs and the tumorigenicity of tumors in nude mice via S1P binding to S1P 3 and down-stream stimulation of Notch and p38 MAPK signaling [49].…”