T. Hanyu1, H. Ichikawa1, T. Ishikawa1, S. Kosugi2, M. Nakajima1, J. Sakata1, T. Kobayashi1, H. Kameyama1, T. Wakai1, M. Nagahashi1 1Niigata University Graduate School Of Medical And Dental Sciences,Division Of Digestive And General Surgery,Niigata, NIIGATA, Japan 2Uonuma Institute Of Community Medicine Niigata University Medical And Dental Hospital,Department Of Digestive And General Surgery,Minami-Uonuma, NIIGATA, Japan
Introduction:
Sphingosine-1-phosphate (S1P), a pleiotropic bioactive lipid mediator, has been implicated as a key regulatory molecule in cancer through its ability to promote cell proliferation, migration, angiogenesis and lymphangiogenesis. Previous studies suggested that S1P produced by sphingosine kinase 1 (SphK1), which is activated by phosphorylation, plays important roles in progression of disease and metastasis. However, the associations between phospho-SphK1 (pSphK1) and clinical parameters in human gastric cancer have not been well investigated to date.
Methods:
We created pSphK1 expression profiles by immunohistochemical analysis for 136 patients, who underwent surgery for gastric cancer at Niigata University Medical and Dental Hospital between January 2007 and December 2009. pSphK1 expression and clinicopathological factors were compared by univariate and multivariate analyses.
Results:
The univariate analysis revealed that pSphK1 expression was significantly correlated with depth of tumor invasion (P = 0.022), lymph node metastasis (P = 0.040), distant metastasis (P = 0.042), histological differentiation (P = 0.048), and lymphatic invasion (P = 0.004). The multivariate analysis revealed that diffuse type (Odds ratio 2.169, 95% confidence interval 1.014–4.630, P = 0.046) and the presence of lymphatic invasion (Odds ratio 3.401, 95% confidence interval 1.451–8.000, P = 0.005) were independently associated with pSphK1 expression in patients with gastric cancer.
Conclusion:
Our results provide the first evidence that pSphK1 expression is associated with invasiveness of human gastric cancer, suggesting importance of S1P in patients with gastric cancer.