PT  - JOURNAL ARTICLE
AU  - NAGARO, HIROKI
AU  - ICHIKAWA, HIROSHI
AU  - TAKIZAWA, KAZUYASU
AU  - NAGAHASHI, MASAYUKI
AU  - ABE, SHUN
AU  - HIROSE, YUKI
AU  - MORO, KAZUKI
AU  - MIURA, KOHEI
AU  - NAKANO, MASATO
AU  - SHIMADA, YOSHIFUMI
AU  - SAKATA, JUN
AU  - WAKAI, TOSHIFUMI
TI  - Clinical Significance of Phosphorylated Sphingosine Kinase 1 Expression in Pancreatic Ductal Adenocarcinoma
AID  - 10.21873/anticanres.16584
DP  - 2023 Sep 01
TA  - Anticancer Research
PG  - 3969--3977
VI  - 43
IP  - 9
4099  - http://ar.iiarjournals.org/content/43/9/3969.short
4100  - http://ar.iiarjournals.org/content/43/9/3969.full
SO  - Anticancer Res2023 Sep 01; 43
AB  - Background/Aim: Sphingosine-1-phosphate (S1P) is a pleiotropic, bioactive, lipid mediator, produced by sphingosine kinase 1 (SphK1). In this study, we evaluated the expression of phosphorylated SphK1 (pSphK1) in patients with pancreatic ductal adenocarcinoma (PDAC) and investigated its clinical significance. Materials and Methods: A total of 111 patients who underwent curative-intent resection for PDAC were enrolled. We investigated pSphK1 (Ser-225) expression in surgically resected specimens of PDAC using immunohistochemistry. The patients were divided into two groups according to pSphK1 immunoreactive expression: a pSphK1-high group (n=63) and a pSphK1-low group (n=48). Results: Logistic regression analyses revealed that lymphatic invasion (p=0.007) was a significantly independent factor associated with high pSphK1 immunoreactive expression. The pSphK1-high group showed significantly worse disease-specific survival (DSS) than the pSphK1-low group (5-year DSS rate, 19.6% vs. 58.7%; p=0.001). High pSphK1 immunoreactive expression (hazard ratio=2.547; 95% confidence interval= 1.434-4.527; p=0.001) was an independent prognostic factor for DSS. Conclusion: High pSphK1 expression is independently associated with lymphatic invasion and unfavorable prognosis in PDAC patients. Thus, the SphK1-S1P axis may be important in mechanisms of tumor progression, such as lymphatic invasion, in PDAC patients.