Expression of Sphingosine-Kinase 1 (SPHK1) as a prognostic factor in ovarian cancer

Objective:

Sphingosine-Kinase 1 (SphK1), encoded by the SPHK1 gene, is a key enzyme of sphingolipid metabolism and overexpressed in a variety of cancer types. In the present study, we investigated the expression of SphK1 and its prognostic impact in ovarian cancers.

Methods:

Tissue micro arrays constructed using formalin-fixed paraffin-embedded tissue of primary ovarian cancers (n = 763) were obtained. Immunohistochemical analysis of SphK1 was performed, and the results were correlated with clinico-pathological characteristics and survival.

Results:

Low SphK1 expression was shown to significantly correlate with optimal tumour resection (p < 0.001). Kaplan-Meier analysis further revealed that low SphK1 levels were associated with improved progression-free survival (PFS; 65,23 months [95% confidence interval (CI): 49,95 – 80,50] vs. 51,42 months [95% CI: 27,02 – 75,82], p = 0,052) and overall-survival (OS; 100,01 months [95%CI: 83,64 – 116,38] vs. 75,35 months [95%CI: 59,85 – 90,85], p = 0,049). Subsequently, the prognostic value of Sphk1 expression together with clinical factors (i.e. FIGO stage, age, and residual tumour burden after surgery) was substantiated in univariate Cox regression analysis (PFS: hazard ratio (HR)= 0,83 [95%CI: 0,69 – 1,00], p = 0,052; OS: HR = 0,82 [95%CI: 0,68 – 1,00], p = 0,05).

Conclusions:

Our results suggest that SphK1 expression might be a prognostic factor in ovarian cancer, and that high SphK1 expression seems to be associated with cancer progression and suboptimal tumour debulking. To corroborate these findings, however, our results need to be validated in an independent patient cohort.