RKIP在下咽癌中的表达及意义
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摘要
目的探讨Raf-1激酶抑制蛋白(Raf-1 kinase inhibitor protein,RKIP)在下咽癌中的表达及其临床意义,通过与癌旁组织RKIP的表达比较,分析RKIP在下咽癌的发生、发展及转移中的作用以及癌旁下咽鳞状上皮中的表达及其临床意义。方法采用免疫组化方法检测46例下咽鳞癌及13例癌旁下咽鳞状上皮组织中RKIP的表达情况。对实验结果进行χ~2检验及Wilcoxon检验。结果 RKIP在下咽鳞癌中的表达低于癌旁下咽鳞状上皮,差异具有统计学意义(P=0.034)。RKIP在有转移的下咽癌中表达低于无转移的下咽癌,差异具有统计学意义(P=0.020)。RKIP在高、中、低不同分化程度的下咽癌中表达阳性率逐渐下降,差异具有统计学意义(P=0.005)。结论下咽癌的分化程度与RKIP的表达有关,下咽癌淋巴结转移的发生与RKIP低表达及缺失有关。
Objective To investigate the expression and clinical significance of Raf-1 kinase inhibitor protein( RKIP) in hypopharyngeal carcinoma. Methods Immunohistochemistry was used to detect the expression of RKIP in 46 specimens of hypopharyngeal carcinoma and 13 of para-carcinoma squamous epithelium. All the results were analyzed with chi-square test and Wilcoxon test. Results The expression of RKIP in the hypopharyngeal carcinoma was lower than that in the para-carcinoma squamous epithelium,and the difference was statistically significant( P = 0. 034). The positive expression rate of RKIP in carcinoma specimens with lymphatic metastasis was lower than that in those without lymphatic metastasis,and the difference was also significant( P = 0. 020). The positive expression rate of RKIP gradually declined from well differentiation to poor differentiation with statistically significant difference( P = 0. 005). Conclusions The differentiation degree of hypopharyngeal carcinoma is associated with the expression of RKIP. And the lymphatic metastasis of hypopharyngeal carcinoma is associated with expression deficiency or down regulation of RKIP.
Objective To investigate the expression and clinical significance of Raf-1 kinase inhibitor protein( RKIP) in hypopharyngeal carcinoma. Methods Immunohistochemistry was used to detect the expression of RKIP in 46 specimens of hypopharyngeal carcinoma and 13 of para-carcinoma squamous epithelium. All the results were analyzed with chi-square test and Wilcoxon test. Results The expression of RKIP in the hypopharyngeal carcinoma was lower than that in the para-carcinoma squamous epithelium,and the difference was statistically significant( P = 0. 034). The positive expression rate of RKIP in carcinoma specimens with lymphatic metastasis was lower than that in those without lymphatic metastasis,and the difference was also significant( P = 0. 020). The positive expression rate of RKIP gradually declined from well differentiation to poor differentiation with statistically significant difference( P = 0. 005). Conclusions The differentiation degree of hypopharyngeal carcinoma is associated with the expression of RKIP. And the lymphatic metastasis of hypopharyngeal carcinoma is associated with expression deficiency or down regulation of RKIP.
引文
[1]彭丽敏,栗妍,朱莉.Raf激酶抑制蛋白与妇科肿瘤间的潜在联系[J].医学综述,2014,20(6):1023-1026.
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[12]Al-Mulla F,Hagan S,Al-Ali W,et al.Raf kinase inhibitor protein:mechanism of loss of expression and association with genomic instability[J].J.Clin.Pathol,2008,61(1):524-529.
[13]Zlobec I,Bihl M,Foerster A,et al.Comprehensive analysis of Cp G island methylator phenotype(CIMP)-high,-low,and-negative colorectal cancers based on protein marker expression and molecular features[J].J Pathol,2011,225(3):336-343.
[14]Guo W,Dong Z,Guo Y,et al.Aberrant methylation and loss expression of RKIP is associated with tumor progression and poor prognosis in gastric cardia adenocarcinoma[J].Clin Exp Metastasis,2013,30(3):265-275.
[15]李冬霞,张慧,汤正,等.胃癌组织中RKIP基因启动子甲基化及蛋白表达[J].临床与实验病理学杂志,2014,30(4):376-378.
[16]Kim HS,Won KY,Kim GY,et al.Reduced expression of Raf-1kinase inhibitory protein predicts regional lymph node metastasis and shorter survival in esophageal squamous cell carcinoma[J].Pathol Res Pract,2012,208(5):292-299.
[17]Fu-Min,Ping,Gui-Jing,et al.Expression of RKIP,E-cadherin and NF-k B p65 in esophageal squamous cell carcinoma and their correlations[J].International journal of clinical and experimental pathology,2015,8(9):10164-10170.
[18]Birner P,Jesch B,Schultheis A,et al.RAF-kinase inhibitor protein(RKIP)downregulation in esophageal cancer and its metastases[J].Clin Exp Metastasis,2012,29(6):551-559.
[19]Wei G,Zhiming D,Yanli G,et al.Aberrant methylation and loss expression of RKIP is associated with tumor progression and poor prognosis in gastric cardia adenocarcinoma[J].Clin Exp Metastasis,2013,30:265-275.
[20]Paola P,Manuela L,Nicoletta V,et al.Analysis of Possible Mechanisms Accounting for Raf-1 Kinase Inhibitor Protein Downregulation in Hepatocellular Carcinoma[J].OMICS A Journal of Integrative Biology,2012,16(11):579-588.
[2]Tang H,Park S,Sun SC,et al.RKIP inhibits NF-kappa B in cancer cells by regulating upstream signaling components of the Ikappa B kinase complex[J].FEBS Lett,2010,584(4):662-668.
[3]褚静,王立芹,曾娟.RKIP基因表达上调对宫颈癌细胞生物学行为影响[J].中国医药导刊,2016,18(8):833-834.
[4]Li FF,Song SJ,Zhang RN.Phosphatidylethanolamine-binding protein(PEBP)in basic and clinical study[J].Sheng Li Ke Xue Jin Zhan,2009,40(3):214-218.
[5]Ammad Ahmad,Farooqi,Yiwei,Li,et al.The biological complexity of RKIP signaling in human cancers[J].Experimental&molecular medicine,2015,4(47):185.
[6]Swadesh KD,Sujita UK,Sokhi,et al.Raf kinase inhibitor RKIP inhibits MDA-9/Syntenin-mediated metastasis in melanoma[J].Cancer Research,2012,72(23):6217-6226.
[7]喻敏,吕农华.Raf激酶抑制蛋白在常见消化系统恶性肿瘤中的研究进展[J].肿瘤,2013,33(4):378-381.
[8]Tang H,Park S,Sun SC,et al.RKIP inhibits NF-kappa B in cancer cells by regulating upstream signaling components of the Ikappa B kinase complex[J].FEBS Lett,2010,584(4):662-668.
[9]Corbit KC,Trakul N,Eves EM,et al.Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein[J].Biol Chem,2003,278(15):13061-13068.
[10]Kroslak T,Koch T,Kahl E,et al.Human phosphatidylethanolamine-binding protein facilitates heterotrimeric G protein-dependent signaling[J].J Biol Chem,2001,276(43):39772-39778.
[11]Lorenz K,Lohse MJ,Quitterer U.Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2[J].Nature,2003,426(6966):574-579.
[12]Al-Mulla F,Hagan S,Al-Ali W,et al.Raf kinase inhibitor protein:mechanism of loss of expression and association with genomic instability[J].J.Clin.Pathol,2008,61(1):524-529.
[13]Zlobec I,Bihl M,Foerster A,et al.Comprehensive analysis of Cp G island methylator phenotype(CIMP)-high,-low,and-negative colorectal cancers based on protein marker expression and molecular features[J].J Pathol,2011,225(3):336-343.
[14]Guo W,Dong Z,Guo Y,et al.Aberrant methylation and loss expression of RKIP is associated with tumor progression and poor prognosis in gastric cardia adenocarcinoma[J].Clin Exp Metastasis,2013,30(3):265-275.
[15]李冬霞,张慧,汤正,等.胃癌组织中RKIP基因启动子甲基化及蛋白表达[J].临床与实验病理学杂志,2014,30(4):376-378.
[16]Kim HS,Won KY,Kim GY,et al.Reduced expression of Raf-1kinase inhibitory protein predicts regional lymph node metastasis and shorter survival in esophageal squamous cell carcinoma[J].Pathol Res Pract,2012,208(5):292-299.
[17]Fu-Min,Ping,Gui-Jing,et al.Expression of RKIP,E-cadherin and NF-k B p65 in esophageal squamous cell carcinoma and their correlations[J].International journal of clinical and experimental pathology,2015,8(9):10164-10170.
[18]Birner P,Jesch B,Schultheis A,et al.RAF-kinase inhibitor protein(RKIP)downregulation in esophageal cancer and its metastases[J].Clin Exp Metastasis,2012,29(6):551-559.
[19]Wei G,Zhiming D,Yanli G,et al.Aberrant methylation and loss expression of RKIP is associated with tumor progression and poor prognosis in gastric cardia adenocarcinoma[J].Clin Exp Metastasis,2013,30:265-275.
[20]Paola P,Manuela L,Nicoletta V,et al.Analysis of Possible Mechanisms Accounting for Raf-1 Kinase Inhibitor Protein Downregulation in Hepatocellular Carcinoma[J].OMICS A Journal of Integrative Biology,2012,16(11):579-588.