甲状腺乳头状癌中SphK1和Annexin A1的表达及意义
摘要
目的探讨鞘氨醇激酶1(sphingosine kinase1,SphK1)和膜联蛋白A1(Annexin A1)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)中的表达及相互关系。方法收集PTC 81例、结节性甲状腺肿(nodular goiter,NG) 30例、癌旁正常甲状腺组织(normal thyroid,NT) 26例。应用免疫组化En Vision两步法检测各组中SphK1和Annexin A1的表达,并分析两者表达与PTC临床病理特征的关系。结果 SphK1和Annexin A1在PTC中的阳性率(60. 5%和61. 7%)高于NG组(33. 3%和26. 7%)以及NT组(30. 8%和23. 1%)(P均<0. 017)。Annexin A1和SphK1表达与PTC淋巴结转移和临床分期相关(P均<0. 01),与患者性别、年龄、部位、肿瘤大小、TG-Ab值和TPO-Ab值无关(P均> 0. 05)。SphK1与Annexin A1表达呈正相关(P <0. 01)。结论 SphK1与Annexin A1可能参与PTC的发生、发展和淋巴结转移,提示二者可能成为甲状腺肿瘤良恶性诊断和早期淋巴结转移风险评估的重要生物学因子。
引文
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[20]Petrella A,Festa M,Ercolino S F,et al.Annexin-1 downregulation in thyroid cancer correlates to the degree of tumour differentiation[J].Cancer Biol Ther,2006,5(6):643-647.
[2]王雪梅,崔亚南,吴琼,等.甲状腺微小乳头状癌发生及淋巴结转移的相关因素分析[J].临床与实验病理学杂志,2013,29(8):909-911.
[3]Kim H S,Yoon G,Ryu J Y,et al.Sphingosine kinase 1 is a reliable prognostic factor and a novel therapeutic target for uterine cervical cancer[J].Oncotarget,2015,6(29):26746.
[4]Li W,Yu C P,Xia J,et al.Sphingosine kinase 1 is associated with gastric cancer progression and poor survival of patients[J].Clin Cancer Res,2009,15(4):1393-1399.
[5]Wang W,Zhong W E N,Chen C,et al.Circulating antibodies to linear peptide antigens derived from ANNEXIN A1 and FOXP3 in lung cancer[J].Anticancer Res,2017,37(6):3151-3155.
[6]Tu Y,Johnstone C N,Stewart A G.Annexin A1 influences in breast cancer:controversies on contributions to tumour,host and immunoediting processes[J].Pharmacol Res,2017,119:278-288.
[7]Edge S B,Compton C C.The American joint committee on cancer:the 7th edition of the AJCC cancer staging manual and the future of TNM[J].Ann Surg Oncol,2010,17(6):1471-1474.
[8]Plano D,Amin S,Sharma A K.Importance of sphingosine kinase(SphK)as a target in developing cancer therapeutics and recent developments in the synthesis of novel SphK inhibitors:miniperspective[J].J Med Chem,2014,57(13):5509-5524.
[9]Lee S O,Kim J S,Lee M S,et al.Anti-cancer effect of pristimerin by inhibition of HIF-1αinvolves the SPHK-1 pathway in hypoxic prostate cancer cells[J].Bmc Cancer,2016,16(1):701.
[10]Maczis M,Milstien S,Spiegel S.Sphingosine-1-phosphate and estrogen signaling in breast cancer[J].Adv Biol Regul,2016,60:160-165.
[11]Akao Y,Banno Y,Nakagawa Y,et al.High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation[J].Biochem Biophys Res Commun,2006,342(4):1284-1290.
[12]Do S I M,Kim H S,Kim K,et al.Predictive value of sphingosine kinase 1 expression in papillary thyroid carcinoma[J].Anticancer Res,2017,37(10):5399-5405.
[13]Zhu Y,You H,Tan J,et al.Overexpression of sphingosine kinase1 is predictive of poor prognosis in human breast cancer[J].Oncol Lett,2017,14(1):63-72.
[14]Liang W,Xie Z,Cui W,et al.Comprehensive gene and microR-NA expression profiling reveals a role for miRNAs in the oncogenic roles of SphK1 in papillary thyroid cancer[J].J Cancer Res Clin Oncol,2017,143(4):601-611.
[15]Monastyrskaya K,Babiychuk E B,Draeger A.The annexins:spatial and temporal coordination of signaling events during cellular stress[J].Cell Mol Life Sci,2009,66(16):2623-2642.
[16]Girol A P,Mimura K K O,Drewes C C,et al.Anti-inflammatory mechanisms of the annexin A1 protein and its mimetic peptide Ac2-26 in models of ocular inflammation in vivo and in vitro[J].J Immunol,2013,190(11):5689-5701.
[17]Pederzoli-Ribeil M,Maione F,Cooper D,et al.Design and characterization of a cleavage-resistant Annexin A1 mutant to control inflammation in the microvasculature[J].Blood,2010,116(20):4288-4296.
[18]Zhang X,Li X,Zheng L,et al.ANXA1 silencing increases the sensitivity of cancer cells to low-concentration arsenic trioxide treatment by inhibiting ERK MAPK activation[J].Tumori,2014,101(4):360-367.
[19]Petrella A,D’Acunto C W,Rodriquez M,et al.Effects of FR235222,a novel HDAC inhibitor,in proliferation and apoptosis of human leukaemia cell lines:role of annexin A1[J].Eur J Cancer,2008,44(5):740-749.
[20]Petrella A,Festa M,Ercolino S F,et al.Annexin-1 downregulation in thyroid cancer correlates to the degree of tumour differentiation[J].Cancer Biol Ther,2006,5(6):643-647.