喉癌组织RKIP基因甲基化表达调控研究
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摘要
目的检测喉癌组织中Raf-1激酶抑制蛋白(Raf-1 kinase inhibitor protein,RKIP)基因启动子区域的甲基化状态及其蛋白表达情况,并探讨其临床意义。方法采用甲基化特异性PCR(methylation-specific PCR,MSP)技术及免疫组化方法检测53例喉癌组织及34例癌旁组织中RKIP基因启动子区域的甲基化状态及蛋白表达情况。结果喉癌及癌旁组织中RKIP基因启动子甲基化发生率分别为17%、3%,两者比较差异具有统计学意义(P=0.045)。结论 RKIP基因启动子区高甲基化状态可能是造成喉癌组织中RKIP表达缺失的分子机制之一,RKIP蛋白表达缺失与喉癌的发生发展及转移有关。
Objective To investigate methylation status in promoter region of raf-1 kinase inhibitor protein( RKIP) gene and the expression of RKIP protein in laryngeal carcinoma,and to discuss their clinical significances. Methods Methylationspecific PCR and immunohistochemistry were used to examine the methylation status of RKIP gene promoter region and the expression of RKIP protein in 53 laryngeal carcinoma tissues and 53 normal adjacent tissues. Results The incidences of RKIP gene promoter methylation in laryngeal carcinoma and adjacent normal tissues were 17% and 3% respectively. The difference was statistically significant( P = 0. 045). Conclusion Promoter hypermethylation of RKIP may be one reason of the deleted expression of RKIP protein,which correlates with occurrence,development and metastasis of laryngeal carcinoma.
Objective To investigate methylation status in promoter region of raf-1 kinase inhibitor protein( RKIP) gene and the expression of RKIP protein in laryngeal carcinoma,and to discuss their clinical significances. Methods Methylationspecific PCR and immunohistochemistry were used to examine the methylation status of RKIP gene promoter region and the expression of RKIP protein in 53 laryngeal carcinoma tissues and 53 normal adjacent tissues. Results The incidences of RKIP gene promoter methylation in laryngeal carcinoma and adjacent normal tissues were 17% and 3% respectively. The difference was statistically significant( P = 0. 045). Conclusion Promoter hypermethylation of RKIP may be one reason of the deleted expression of RKIP protein,which correlates with occurrence,development and metastasis of laryngeal carcinoma.
引文
[1]Tang H,Park S,Sun S C,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.
[2]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(8):524-529.
[3]许良中,杨文涛.免疫组织化学反应结果的判断标准[J].中国癌症杂志,1996,6(4):229-231.
[4]Andy J,Minn E,Bevilacqua J,et al.Identification of novel metastasis suppressor signaling pathways for breast cancer[J].Cell cycle,2012,11(13):2452-2457.
[5]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.
[6]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(4):265-275.
[7]Parham M,Inti Z,Kristi B,et al.Loss of Raf-1 Kinase Inhibitor Protein Expression Is Associated With Tumor Progression and Metastasis in Colorectal Cancer[J].American Society for Clinical Pathology,2007,127(9):820-827.
[8]Olga M,António G,Paula S,et al.Loss of RKIP expression is associated with poor survival in GISTs[J].Virchows Arch,2009,455(4):277-284.
[9]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.
[10]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.
[11]魏红,张向阳,魏东敏,等.食管鳞状细胞癌RKIP基因甲基化状态的检测及临床意义[J].现代中西医结合杂志,2012,21(21):2281-2284.
[12]齐战,杨大运.肺癌组织中RKIP基因启动子区甲基化状态观察[J].山东医药,2011,51(46):70-71.
[2]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(8):524-529.
[3]许良中,杨文涛.免疫组织化学反应结果的判断标准[J].中国癌症杂志,1996,6(4):229-231.
[4]Andy J,Minn E,Bevilacqua J,et al.Identification of novel metastasis suppressor signaling pathways for breast cancer[J].Cell cycle,2012,11(13):2452-2457.
[5]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.
[6]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(4):265-275.
[7]Parham M,Inti Z,Kristi B,et al.Loss of Raf-1 Kinase Inhibitor Protein Expression Is Associated With Tumor Progression and Metastasis in Colorectal Cancer[J].American Society for Clinical Pathology,2007,127(9):820-827.
[8]Olga M,António G,Paula S,et al.Loss of RKIP expression is associated with poor survival in GISTs[J].Virchows Arch,2009,455(4):277-284.
[9]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.
[10]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.
[11]魏红,张向阳,魏东敏,等.食管鳞状细胞癌RKIP基因甲基化状态的检测及临床意义[J].现代中西医结合杂志,2012,21(21):2281-2284.
[12]齐战,杨大运.肺癌组织中RKIP基因启动子区甲基化状态观察[J].山东医药,2011,51(46):70-71.