磷酸鞘氨醇激酶 1 在胰腺导管腺癌中的表达的临床意义。

Clinical Significance of Phosphorylated Sphingosine Kinase 1 Expression in Pancreatic Ductal Adenocarcinoma.

机构信息

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan;

出版信息

Anticancer Res. 2023 Sep;43(9):3969-3977. doi: 10.21873/anticanres.16584.

DOI:10.21873/anticanres.16584

PMID:37648331

Abstract

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.

摘要

背景/目的：鞘氨醇-1-磷酸（S1P）是一种多效、生物活性的脂质介质，由鞘氨醇激酶 1（SphK1）产生。在这项研究中，我们评估了磷酸化 SphK1（pSphK1）在胰腺导管腺癌（PDAC）患者中的表达，并研究了其临床意义。

材料和方法

共纳入 111 例接受根治性手术治疗的 PDAC 患者。我们使用免疫组织化学法检测手术切除的 PDAC 标本中 pSphK1（Ser-225）的表达。根据 pSphK1 免疫反应性表达，将患者分为两组：pSphK1 高组（n=63）和 pSphK1 低组（n=48）。

结果

逻辑回归分析显示，淋巴浸润（p=0.007）是与高 pSphK1 免疫反应性表达显著相关的独立因素。pSphK1 高组的疾病特异性生存率（DSS）明显低于 pSphK1 低组（5 年 DSS 率，19.6% vs. 58.7%；p=0.001）。高 pSphK1 免疫反应性表达（危险比=2.547；95%置信区间=1.434-4.527；p=0.001）是 DSS 的独立预后因素。