Abstract
PurposeSphingosine-kinase-1 (SPHK1) is a key enzyme of sphingolipid metabolism which is involved in ovarian cancer pathogenesis, progression and mechanisms of drug resistance. It is overexpressed in a variety of cancer subtypes. We investigated SPHK1 expression as a prognostic factor in epithelial ovarian cancer patients.MethodsExpression analysis of SPHK1 was performed on formalin-fixed paraffin-embedded tissue from 1005 ovarian cancer patients with different histological subtypes using immunohistochemistry. Staining intensity of positive tumor cells was assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival.ResultsIn our ovarian cancer collective, high levels of SPHK1 expression correlated significantly with complete surgical tumor resection (p = 0.002) and lower FIGO stage (p = 0.04). Progression-free and overall survival were further significantly longer in patients with high-grade serous ovarian cancer and overexpression of SPHK1 (p = 0.002 and p = 0.006, respectively).ConclusionOur data identify high levels of SPHK1 expression as a potential favorable prognostic marker in ovarian cancer patients.
Highlights
Epithelial ovarian cancer (EOC) remains the fifth most common lethal cancer in women
The SPHK1 receptor signaling pathway has been implicated in a variety of pathological processes of ovarian cancer in vitro (Dai et al 2017)
Molecular markers like SPHK1 can potentially serve as diagnostic as well as prognostic and predictive markers. This is the first report on an association of prognosis and SPHK1 in ovarian cancer
Summary
Epithelial ovarian cancer (EOC) remains the fifth most common lethal cancer in women. A variety of different signaling pathways and their respective metabolites have been associated with mechanisms of tumor pathogenesis and progression, and the expression of. Sphingolipid metabolism is one of these pathogenetic pathways involved in both inflammatory and oncological disease. The balance between the intracellular levels of these sphingolipids is controlled by the key enzymes which produce or degrade these metabolites. Ceramide is converted into sphingosine that, in turn, is phosphorylated by a sphingosine kinase (SPHK; two isoforms SPHK1 and SPHK2) to form S1P During this process, phosphorylation of sphingosine is a rate-limiting step in the sphingolipid metabolism. S1P is involved in the regulation of key cellular processes that contribute to ovarian cancer initiation and progression. Inhibition of the S1P signaling pathway has been proposed to inhibit ovarian cancer cell growth and induce apoptosis. S1P has been suggested as a potential molecular target for ovarian cancer therapy (Dai et al 2014; Dai et al 2017)
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