磷酸神经鞘氨醇在胃癌中的表达及临床意义
|
摘要
目的探讨磷酸神经鞘氨醇(S1P)在胃癌组织中的表达及其临床意义。方法采用实时荧光定量PCR和免疫组织化学染色检测60例胃癌组织及其癌旁正常胃黏膜组织中S1P和S1P受体1(S1PR1)的表达,分析血清S1P表达与胃癌患者预后的关系。结果 S1P和S1PR1在胃癌组织中的表达均高于癌旁正常胃黏膜组织(P<0.01)。S1P表达与S1PR1和IL-6表达均呈正相关(r=0.304和0.241,P<0.01)。胃癌患者血清S1P的表达与术后累积生存率呈负相关(HR=2.246,P<0.01)。结论 S1P在胃癌组织中高表达,在胃癌进展中发挥重要作用,有望成为胃癌预后判断和治疗的新靶点。
Objective To investigate the expression and clinical significance of sphingosine1-phosphate(S1P)in human gastric cancer.Methods The expressions of S1 Pand its receptor S1PR1 were detected by real-time fluorescent quantitative PCR and immunohistochemistry in 60 cases of gastric cancer tissues and its tumor-adjacent normal tissues.And the relationship between serum S1 P expression and prognosis of the patients with gastric cancer was analyzed.Results The expressions of S1 Pand S1PR1in gastric cancer tissues were higher than those in tumor-adjacent normal tissues(P<0.01).S1 Pexpression was positively correlated with S1PR1 and IL-6expressions(r=0.304and0.241,P<0.01).Serum S1 Pexpression was negatively relevant to the cumulative survival rate after operation in the patients with gastric cancer(HR=2.246,P<0.01).Conclusion S1 Pis highly expressed in gastric cancer tissues,which plays an important role in the development of gastric cancer and may hopefully serve as a new target for therapy and an indicator for the prediction of prognosis.
Objective To investigate the expression and clinical significance of sphingosine1-phosphate(S1P)in human gastric cancer.Methods The expressions of S1 Pand its receptor S1PR1 were detected by real-time fluorescent quantitative PCR and immunohistochemistry in 60 cases of gastric cancer tissues and its tumor-adjacent normal tissues.And the relationship between serum S1 P expression and prognosis of the patients with gastric cancer was analyzed.Results The expressions of S1 Pand S1PR1in gastric cancer tissues were higher than those in tumor-adjacent normal tissues(P<0.01).S1 Pexpression was positively correlated with S1PR1 and IL-6expressions(r=0.304and0.241,P<0.01).Serum S1 Pexpression was negatively relevant to the cumulative survival rate after operation in the patients with gastric cancer(HR=2.246,P<0.01).Conclusion S1 Pis highly expressed in gastric cancer tissues,which plays an important role in the development of gastric cancer and may hopefully serve as a new target for therapy and an indicator for the prediction of prognosis.
引文
[1]Arlt O,Schwiebs A,Japtok L,et al.Sphingosine-1-phosphate modulates dendritic cell function:focus on non-migratory effects in vitro and in vivo[J].Cell Physiol Biochem,2014,34(1):27-44.
[2]Kono M,Proia RL.Imaging S1P1activation in vivo[J].Exp Cell Res,2015,333(2):178-182.
[3]Zhao J,Garcia D,Gartung A,et al.Sphingosine-1-phosphate receptor subtype 2signaling in endothelial senescence-associated functional impairments and inflammation[J].Curr Atheroscler Rep,2015,17(5):504.
[4]Carr JM,Mahalingam S,Bonder CS,et al.Sphingosine kinase1in viral infections[J].Rev Med Virol,2013,23(2):73-84.
[5]Chi H.Sphingosine-1-phosphate and immune regulation:trafficking and beyond[J].Trends Pharmacol Sci,2011,32(1):16-24.
[6]Cusack KP,Stoffel RH.S1P(1)receptor agonists:assessment of selectivity and current clinical activity[J].Curr Opin Drug Discov Devel,2010,13(4):481-488.
[7]Adada M,Canals D,Hannun YA,et al.Sphingosine-1-phosphate receptor 2[J].FEBS J,2013,280(24):6354-6366.
[8]Adan-Gokbulut A,Kartal-Yandim M,Iskender G,et al.Novel agents targeting bioactive sphingolipids for the treatment of cancer[J].Curr Med Chem,2013,20(1):108-122.
[9]Aoyagi T,Nagahashi M,Yamada A,et al.The role of sphingosine-1-phosphate in breast cancer tumor-induced lymphangiogenesis[J].Lymphat Res Biol,2012,10(3):97-106.
[10] Garris CS,Wu L,Acharya S,et al.Defective sphingosine1-phosphate receptor 1(S1P1)phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation[J].Nat Immunol,2013,14(11):1166-1172.
[11] Lee H,Deng J,Kujawski M,et al.STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors[J].Nat Med,2010,16(12):1421-1428.
[12] Poti F,Costa S,Bergonzini V,et al.Effect of sphingosine1-phosphate(S1P)receptor agonists FTY720and CYM5442on atherosclerosis development in LDL receptor deficient(LDL-R-/-)mice[J].Vascul Pharmacol,2012,57(1):56-64.
[2]Kono M,Proia RL.Imaging S1P1activation in vivo[J].Exp Cell Res,2015,333(2):178-182.
[3]Zhao J,Garcia D,Gartung A,et al.Sphingosine-1-phosphate receptor subtype 2signaling in endothelial senescence-associated functional impairments and inflammation[J].Curr Atheroscler Rep,2015,17(5):504.
[4]Carr JM,Mahalingam S,Bonder CS,et al.Sphingosine kinase1in viral infections[J].Rev Med Virol,2013,23(2):73-84.
[5]Chi H.Sphingosine-1-phosphate and immune regulation:trafficking and beyond[J].Trends Pharmacol Sci,2011,32(1):16-24.
[6]Cusack KP,Stoffel RH.S1P(1)receptor agonists:assessment of selectivity and current clinical activity[J].Curr Opin Drug Discov Devel,2010,13(4):481-488.
[7]Adada M,Canals D,Hannun YA,et al.Sphingosine-1-phosphate receptor 2[J].FEBS J,2013,280(24):6354-6366.
[8]Adan-Gokbulut A,Kartal-Yandim M,Iskender G,et al.Novel agents targeting bioactive sphingolipids for the treatment of cancer[J].Curr Med Chem,2013,20(1):108-122.
[9]Aoyagi T,Nagahashi M,Yamada A,et al.The role of sphingosine-1-phosphate in breast cancer tumor-induced lymphangiogenesis[J].Lymphat Res Biol,2012,10(3):97-106.
[10] Garris CS,Wu L,Acharya S,et al.Defective sphingosine1-phosphate receptor 1(S1P1)phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation[J].Nat Immunol,2013,14(11):1166-1172.
[11] Lee H,Deng J,Kujawski M,et al.STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors[J].Nat Med,2010,16(12):1421-1428.
[12] Poti F,Costa S,Bergonzini V,et al.Effect of sphingosine1-phosphate(S1P)receptor agonists FTY720and CYM5442on atherosclerosis development in LDL receptor deficient(LDL-R-/-)mice[J].Vascul Pharmacol,2012,57(1):56-64.