CXCR5/CXCL13及ERK1在甲状腺乳头状癌中的表达及意义
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摘要
目的:观察甲状腺乳头状癌及其转移灶中CXCR5/CXCL13及ERK1的表达,探讨其在肿瘤发生发展中的可能作用。方法:选取2014年1月到2016年5月在本院进行手术的110例甲状腺乳头状癌患者及同期手术的结节性甲状腺肿患者,采用免疫组化法检测CXCR5/CXCL13及ERK1在甲状腺乳头状癌及其转移灶中的表达量。结果:CXCL13、CXCR5及ERK1在甲状腺乳头状癌及其转移淋巴结中的表达均高于正常腺体组织及结节性甲状腺肿患者(P<0.05)。CXCL13、CXCR5及ERK1蛋白在甲状腺乳头状癌中的表达与年龄和性别无关,与淋巴结转移呈正相关(P<0.05)。CXCR5/CXCL13蛋白的表达与ERK1呈正相关。结论:趋化因子CXCL13及其受体CXCR5在甲状腺乳头状癌发生发展及其淋巴结转移中发挥了重要作用,为临床甲状腺乳头状癌的诊断及靶向治疗提供一定的理论依据。
Objective: To investigate the expression of CXCR5/CXCL13 and ERK1, and to explore the possible role of occurrence and development in papillary thyroid carcinoma and the lymph node metastases. Methods : Totally110 patients with papillary thyroid carcinoma and other 10 patients with nodular goiter who underwent surgery in our hospital from January 2014 to May 2016 were enrolled in this study. Immunohistochemistry was used to detect the expression of CXCR5/CXCL13 and ERKI in papillary thyroid carcinoma and lymph node metastases. Results:The expressions of CXCL13,CXCR5 and ERKI in papillary thyroid carcinoma and metastatic lymph nodes were significantly higher than those in normal glandular tissue and nodular goiter(P <0. 05). The expression of CXCL13, CXCR5 and ERK1 in papillary thyroid carcinoma was not related to age and gender, and positively correlated with lymph node metastasis(P <0. 05). The expression of CXCR5/CXCL13 protein was positively correlated with ERK1. Conclusion:The chemokine CXCL13 and its receptor CXCR5 play an important role in the development of papillary thyroid carcinoma and its lymph node metastasis, and provide a theoretical basis for the diagnosis and targeted therapy of papillary thyroid carcinoma.
Objective: To investigate the expression of CXCR5/CXCL13 and ERK1, and to explore the possible role of occurrence and development in papillary thyroid carcinoma and the lymph node metastases. Methods : Totally110 patients with papillary thyroid carcinoma and other 10 patients with nodular goiter who underwent surgery in our hospital from January 2014 to May 2016 were enrolled in this study. Immunohistochemistry was used to detect the expression of CXCR5/CXCL13 and ERKI in papillary thyroid carcinoma and lymph node metastases. Results:The expressions of CXCL13,CXCR5 and ERKI in papillary thyroid carcinoma and metastatic lymph nodes were significantly higher than those in normal glandular tissue and nodular goiter(P <0. 05). The expression of CXCL13, CXCR5 and ERK1 in papillary thyroid carcinoma was not related to age and gender, and positively correlated with lymph node metastasis(P <0. 05). The expression of CXCR5/CXCL13 protein was positively correlated with ERK1. Conclusion:The chemokine CXCL13 and its receptor CXCR5 play an important role in the development of papillary thyroid carcinoma and its lymph node metastasis, and provide a theoretical basis for the diagnosis and targeted therapy of papillary thyroid carcinoma.
引文
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[3]Zlotnik A,Yoshie O.The chemokine superfamily revisited[J].Immunity,2012,36(5):705-716.
[4]Grbic DM,Degagne E,Langlois C,et al.Intestinal inflammation increases the expression of the P2Y6 receptor on epithelial cells and the release of CXC chemokine ligand 8 by UDP[J].J Immumol,2008,180(4):2659-2668.
[5]Lukacs-Kornek V,Engel D,Tacke F,et al.The role of chemokines and their receptors in dendritic cell biology[J].Front Biosci,2008,13:2238-2252.
[6]Legler DF,Loetscher M,Roos RS,et al.B cell-attracting chemokine 1,a human CXC chemokine expressed in lymphoid tissues,selectively attracts B lymphocytes via BLR1/CXCR5[J].Exp Med,1998,187(4):655-660.
[7]Moreth K,Brodbeck R,Babelova A,et al.The proteoglycan biglycan regulates expression of the B cell chemoattractant CXCL13 and aggravates murine lupus nephritis[J].J Clin Invest,2010,120(12):4251-4272.
[8]Müller G,H9pken UE,Lipp M.The impact of CCR7 and CXCR5on lymphoid organ development and systemic immunity[J].Immunol Rev,2003,195:117-135.
[9]Sambandam Y,Sundaram K,Liu A,et al.CXCL13 activation of cMyc induces RANK ligand expression in stromal/preosteoblast cells in the oral squamous cell carcinoma tumor-bone microenvironment[J].Oncogene,2013,32(1):97-105.
[10]Van de Pavert SA,Olivier BJ,Goverse G,et al.Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation[J].Nat Immunol,2009,10(11):1193-1199.
[11]Razis E,Kalogeras KT,Kotoula V,et al.Improved outcome of high-risk early HER2 positive breast cancer with high CXCL13-CXCR5 messenger RNA expression[J].Clin Breast Cancer,2012,12(3):183-193.
[12]Meijer J,Zeelenberg IS,Sipos B,et al.The CXCR5 chemokine receptor is expressed by carcinoma cells and promotes growth of colon carcinoma in the liver[J].Cancer Res,2006,66(19):9576-9582.
[13]Liu YK,You QJ,Jin LF,et al.Relationship of CXCR5-CXCL13expressing and colorectal carcinoma metastasis together with KRAS mutation[J].Shandong Medical Journal,2014(34):1-4.
[14]Keshet Y,Seger R.The MAP kinase signaling cascades:A system of hundreds of components regulates a diverse array of physiological functions[J].Methods Mol Biol,2010,661:3-38.
[15]Boulton TG,Nye SH,Robbins DJ,et al.ERKs:A family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to in sulin and NGF[J].Cell,1991,65(4):663-675.
[16]Ree PL,Goldberg RJ,Ray EC,et al.Inhibition of extracellular signal-regulated kinase l/2 Phos Phorylation and induetion of apotosis by sulindac metabolites[J].Caneer Res,2001,61(4):1541-1547.
[17]Marinissen MJ,Gutkind JS.G-protein-coupled receptors and signaling networks:Emerging paradigms[J].Trends Pharmacol Sci,2001,22(7):368-376.
[18]Burger JA,Tsukada N,Burger M,et al.Blood-derived nurselike cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1[J].Blood,2000,96(8):2655-2663.
[19]Ma YY,Huang Y,Yan LL,et al.Role of ERK transduction signaling pathway in proliferation and invasion of endometrial carcinoma cells promoted by CXCL12[J].Chin J Cancer Biother,2016,23(2):250-254.