Predictive and prognostic value of sphingosine kinase 1 expression in patients with invasive ductal carcinoma of the breast.

ABSTRACT

Sphingosine kinase 1 (SPHK1) has been found to be upregulated in many different types of human malignancy and plays a crucial role in cancer development and progression. However, the potential of SPHK1 to act as a predictive and prognostic biomarker in breast cancer remains to be clarified. In the present study, SPHK1 expression was evaluated in breast cancer cell lines and 224 breast cancer tissue samples using immunohistochemical staining. Compared to the normal mammary epithelial cell line MCF-10A, SPHK1 mRNA and protein expression levels increased in the breast cancer cell lines SK-BR-3, MDA-MB-231, MDA-MB-436, and MCF-7. Immunohistochemical staining revealed SPHK1 expression to be significantly increased in breast cancer tissue compared to normal breast tissue, with 85 (37.9%) of the 224 invasive ductal carcinomas (IDC) exhibiting high SPHK1 expression. High SPHK1 expression in IDC showed a significant association with higher histological grade, distant metastasis, and triple negativity, and was shown to be an independent predictor for distant metastasis development. In addition, patients with high SPHK1 expression had significantly lower progression-free survival and overall survival rates compared to those with low SPHK1 expression. Our data suggest that SPHK1 is involved in the development and progression of breast cancer and can serve as a potential predictive biomarker of distant metastasis and patient outcome.