Expression of phosphorylated sphingosine kinase 1 is associated with diffuse type and lymphatic invasion in human gastric cancer
Expression of phosphorylated sphingosine kinase 1 is associated with diffuse type and lymphatic invasion in human gastric cancer
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DOI：
10.1016/j.surg.2017.11.024
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发表时间：
2018-06-01
期刊：
影响因子：
3.8
通讯作者：
Wakai, Toshifumi
中科院分区：
文献类型：
--
作者：
Hanyu, Takaaki;Nagahashi, Masayuki;Wakai, Toshifumi
背景：鞘氨醇-L-磷酸是一种多效性生物活性脂质介体，在肿瘤进展中起重要作用。以往的研究表明，鞘氨醇激酶1产生的鞘氨醇-L-磷酸被磷酸化激活，在疾病的发展和转移中发挥重要作用。鞘氨醇激酶1产生的磷酸鞘氨醇-L-磷酸与胃癌临床参数之间的关系尚未得到充分的研究。方法：通过免疫组织化学方法，建立鞘氨醇激酶产生的磷酸-鞘氨醇-L-磷酸表达谱。结果：单因素分析显示，鞘氨醇激酶表达产生的磷酸鞘氨醇-1-磷酸与肿瘤的侵袭深度、淋巴结转移、远处转移、组织学类型、淋巴侵犯密切相关。多因素分析显示弥漫型(优势比2.210；95%可信区间1.045-4.671，P=.038)和淋巴侵犯(优势比3.697；95%可信区间1.161-8.483，P=0.002)与胃癌鞘氨醇激酶表达产生的1-磷酸鞘氨醇独立相关。鞘氨醇激酶阳性表达产生的1-磷酸鞘氨醇-L和鞘氨醇激酶阴性表达产生的磷酸-鞘氨醇-1-磷酸患者的5年疾病特异性生存率分别为79.3%和98.3%(P=0.002)。然而，在多变量分析中，由鞘氨醇激酶表达产生的高磷酸鞘氨醇不是疾病特异性生存的独立预后因素(风险比5.540；95%可信区间，0.717-42.81，P=.100)。结论：我们首次提供证据表明，胃癌患者弥漫性组织学类型和淋巴侵犯与鞘氨醇激酶表达产生的高磷酸鞘氨醇-1-磷酸L独立相关，提示神经鞘氨醇-L-磷酸在胃癌患者的疾病进展中起作用。(C)2017 Elsevier Inc.保留所有权利。
Background: Sphingosine-l-phosphate, a pleiotropic bioactive lipid mediator, is an important player in cancer progression. Previous studies suggested that sphingosine-l-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-l-phosphate produced by sphingosine kinase 1 and clinical parameters in human gastric cancer have not been fully investigated to date.Methods: We created phospho-sphingosine-l-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.Results: The univariate analysis revealed that phospho-sphingosine-l-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-l-phosphate produced by sphingosine kinase-positive expression and 98.3% in those with phospho-sphingosine-l-phosphate produced by sphingosine kinase-negative expression (P=.002). In multivariate analysis, however, high phosphosphingosine-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).Conclusion: We provide the first evidence that diffuse histologic type and lymphatic invasion were independently associated with high phospho-sphingosine-l-phosphate produced by sphingosine kinase expression in gastric cancer patients, indicating a role of sphingosine-l-phosphate in disease progression among patients with gastric cancer. (C) 2017 Elsevier Inc. All rights reserved.