Increased Sphingosine Kinase 1 Expression Predicts Distant Metastasis and Poor Outcome in Patients With Colorectal Cancer

Abstract

BACKGROUND/AIM: Sphingosine kinase 1 (SPHK1) is up-regulated in many different cancers and plays a crucial role in tumor development and progression. However, the prognostic value of SPHK1 in colorectal cancer (CRC) remains unclear.

MATERIALS AND METHODS: The expression of SPHK1 in CRC cell lines and 328 CRC tissue samples was examined. It was also investigated whether SPHK1 expression is associated with clinicopathological characteristics and outcomes in patients with CRC.

RESULTS: HCT 116 and HT-29 cells expressed significantly higher SPHK1 levels than did CCD 841 CoTr. On immunohistochemistry, SPHK1 expression was significantly higher in CRC tissue than in normal colonic mucosal tissue, with 34.1% of CRC patients exhibiting high SPHK1 expression. High SPHK1 expression in CRC was significantly associated with higher histological grade, deeper invasion depth, lymphatic invasion, vascular invasion, and development of distant metastasis, and was shown to be an independent predictor of distant metastasis. Furthermore, patients with high SPHK1 expression had significantly lower overall survival rates than those with low expression.

CONCLUSION: High SPHK1 expression was significantly associated with aggressive CRC behavior and worse overall survival, and was an independent predictor of distant metastasis. SPHK1 may thus be a potential prognostic biomarker and therapeutic target in CRC patients.