Increased Sphingosine Kinase 1 Expression Is Associated with Poor Prognosis in Human Solid Tumors: A Meta-Analysis

Abstract

Background and Aim. Sphingosine kinase 1 (SPHK1) is a key enzyme of sphingolipid metabolism which is involved in the pathogenesis and progression of human cancer. It has been demonstrated to be upregulated in various types of human malignancies. However, the prognostic value of SPHK1 remains unclear. Therefore, we performed this meta-analysis to assess its predictive value in the prognosis of cancer patients. Methods. PubMed, Web of Science, Embase, CNKI, and Wanfang databases were thoroughly searched for eligible studies, in which the relationship between SPHK1 expression and cancer prognosis was evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to estimate the impact of SPHK1 expression on cancer patients’ survival. Odds ratios (ORs) and 95% CIs were combined to assess the association between SPHK1 expression and clinicopathological characteristics of cancer patients. The certainty of evidence was evaluated by Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Results. Thirty studies comprising 32 cohorts with 5965 patients were included in this meta-analysis. The outcomes indicated that elevated SPHK1 expression was associated with worse overall survival (OS) ( $\text{HR}=1.71$ , 95% CI: 1.45-2.01, $P<0.001$ ) and disease-free survival (DFS) ( $\text{HR}=1.34$ , 95% CI: 1.13-1.59, $P=0.001$ ). What is more, SPHK1 overexpression was significantly correlated with certain phenotypes of tumor aggressiveness, such as clinical stage ( $\text{OR}=2.07$ , 95% CI: 1.39-3.09, $P<0.001$ ), tumor invasion ( $\text{OR}=2.16$ , 95% CI: 1.47-3.18, $P<0.001$ ), lymph node metastasis ( $\text{OR}=2.04$ , 95% CI: 1.71-2.44, $P<0.001$ ), and distant metastasis ( $\text{OR}=3.16$ , 95% CI: 2.44-4.09, $P<0.001$ ). The quality of the evidence for both OS and DFS was low. Conclusions. Increased SPHK1 expression is related to poor prognosis in human cancers and may serve as a promising prognostic marker and therapeutic target for malignant patients. However, conclusions need to be treated with caution because of lack of high quality of evidence.