Expression of phosphorylated sphingosine kinase 1 is associated with diffuse type and lymphatic invasion in human...

Sphingosine-1-phosphate, a pleiotropic bioactive lipid mediator, is an important player in cancer progression. Previous studies suggested that sphingosine-1-phosphate produced by sphingosine kinase 1, which is activated by phosphorylation, plays important roles in the progression of disease and metastasis. The association between phospho-sphingosine-1-phosphate produced by sphingosine kinase 1 and clinical parameters in human gastric cancer have not been fully investigated to date.

We created phospho-sphingosine-1-phosphate produced by sphingosine kinase expression profiles by immunohistochemistry for 136 patients who underwent operative intervention for gastric cancer in 2007-2009. Phospho-sphingosine-1-phosphate produced by sphingosine kinase expression and compared clinicopathologic factors by univariate and multivariate analyses.

The univariate analysis revealed that phospho-sphingosine-1-phosphate produced by sphingosine kinase expression was correlated significantly with depth of tumor invasion, lymph node metastasis, distant metastasis, histologic type, and lymphatic invasion. The multivariate analysis revealed that the diffuse type (odds ratio 2.210; 95% confidence interval, 1.045-4.671, P=.038) and the presence of lymphatic invasion (odds ratio 3.697; 95% confidence interval, 1.161-8.483, P=.002) were associated independently with phospho-sphingosine-1-phosphate produced by sphingosine kinase expression in patients with gastric cancer. The 5-year rate of disease-specific survival was 79.3% in patients with phospho-sphingosine-1-phosphate produced by sphingosine kinasephospho-sphingosine-1-phosphate produced by sphingosine kinase-positive expression and 98.3% in those with phospho-sphingosine-1-phosphate produced by sphingosine kinase-negative expression (P=.002). In multivariate analysis, however, high phospho-sphingosine-1-phosphate produced by sphingosine kinase expression was not an independent prognostic factor for disease-specific survival (hazard ratio 5.540; 95% confidence interval, 0.717-42.81, P=.100).

We provide the first evidence that diffuse histologic type and lymphatic invasion were independently associated with high phospho-sphingosine-1-phosphate produced by sphingosine kinase expression in gastric cancer patients, indicating a role of sphingosine-1-phosphate in disease progression among patients with gastric cancer. (Surgery 2017;160:XXX-XXX.).