RUNX3、β-catenin、C-myc在结直肠腺瘤癌变中的作用
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摘要
目的检测人类runt相关转录因子基因(RUNX3)、β-连珠蛋白(β-catenin)、原癌基因(C-myc)在结直肠腺瘤癌变中的表达,探讨其在结直肠癌变中的作用。方法回顾性分析2014年1月—2016年1月首都医科大学附属北京潞河医院结直肠腺瘤癌变病例57例(结直肠瘤癌变组),另外选择结直肠腺瘤33例(结直肠腺瘤组),正常结直肠黏膜20例(正常组织组)。应用免疫组织化学的方法分别检测RUNX3、β-catenin、C-myc在结直肠腺瘤癌变组、结直肠腺瘤组及正常组织组中的表达情况。结果 RUNX3在结直肠腺瘤癌变组的阳性表达率显著低于结直肠腺瘤组及正常组织组(χ~2=29.788,P=0.000);β-catenin、C-myc在结直肠腺瘤癌变组阳性表达率显著高于腺瘤组及正常组(χ~2=24.338、52.711,P均=0.000)。在结直肠腺瘤癌变组中,RUNX3与β-catenin呈负相关(r=-0.475,P=0.000);β-catenin与C-myc呈正相关(r=0.362,P=0.006);RUNX3与C-myc无相关性(r=-0.200,P=0.136)。结论 RUNX3在结直肠腺瘤癌变组表达下调,从而影响β-catenin、C-myc表达上调,RUNX3、β-catenin、C-myc在结直肠腺瘤癌变中具有重要作用。
Objective To detect the expression of RUNX3,β-catenin and C-myc in carcinogenesis of colorectal adenoma and to explore its role in colorectal carcinogenesis. Methods Retrospective analyze 57 cases of colorectal adenocarcinoma in Beijing Luhe Hospital,Capital Medical University from January 2014 to January 2016. The expressions of RUNX3,β-catenin and C-myc were detected by immunohistochemistry methods in colorectal adenocarcinoma,colorectal adenoma group and normal group. Results The positive expression rate of RUNX3 in colorectal adenocarcinoma was significantly lower than that in adenoma group and normal group( χ~2= 29. 788,P = 0. 000); The positive expression rate of β-catenin and C-myc in colorectal adenocarcinoma was significantly higher than that in adenoma group and normal group( β-catenin: χ~2= 24. 338,P = 0. 000; C-myc: χ~2= 52. 711,P = 0. 000). The expression rate of RUNX3 and β-catenin was negatively correlated( r =-0. 475,P = 0. 000); The expression of β-catenin and C-myc was positively correlated( r = 0. 362,P = 0. 006). The expression rate of RUNX3 and C-myc was not correlated( r =-0. 200,P = 0. 136). Conclusion The RUNX3 was lowered in colorectal adenocarcinoma,which affects the expression of β-catenin and C-myc. RUNX3,β-catenin and C-myc play an important role in the carcinogenesis of colorectal adenoma.
Objective To detect the expression of RUNX3,β-catenin and C-myc in carcinogenesis of colorectal adenoma and to explore its role in colorectal carcinogenesis. Methods Retrospective analyze 57 cases of colorectal adenocarcinoma in Beijing Luhe Hospital,Capital Medical University from January 2014 to January 2016. The expressions of RUNX3,β-catenin and C-myc were detected by immunohistochemistry methods in colorectal adenocarcinoma,colorectal adenoma group and normal group. Results The positive expression rate of RUNX3 in colorectal adenocarcinoma was significantly lower than that in adenoma group and normal group( χ~2= 29. 788,P = 0. 000); The positive expression rate of β-catenin and C-myc in colorectal adenocarcinoma was significantly higher than that in adenoma group and normal group( β-catenin: χ~2= 24. 338,P = 0. 000; C-myc: χ~2= 52. 711,P = 0. 000). The expression rate of RUNX3 and β-catenin was negatively correlated( r =-0. 475,P = 0. 000); The expression of β-catenin and C-myc was positively correlated( r = 0. 362,P = 0. 006). The expression rate of RUNX3 and C-myc was not correlated( r =-0. 200,P = 0. 136). Conclusion The RUNX3 was lowered in colorectal adenocarcinoma,which affects the expression of β-catenin and C-myc. RUNX3,β-catenin and C-myc play an important role in the carcinogenesis of colorectal adenoma.
引文
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[18]李超,许芝林,赵峥.K-ras基因与C-myc基因在大肠癌中的表达及相关性研究[J].哈尔滨医科大学学报,2009,43(6):572-575.DOI:10.3969/j.issn.1000-1905.2009.06.012.
[19]颜景旺,杜太平.Runx3基因Cp G岛甲基化在结肠癌病情及预后评估中的价值[J].临床著作,2017,4(20):287-290.DOI:10.3969/j.issn.1009-9905.2017.04.010.
[20]Kriegl L,Vieth M,Kirchner T,et al.Up-regulation of c-MYC and SIRT1 expression correlated with malignant transformation in the serrated route to colorectal cancer[J].Oncotarget,2012,3:1182-1193.DOI:10.18632/oncotarget.628.
[2]来茂德.个体化治疗时代的结直肠癌病理诊断[J].中华病理学杂志,2014,43(2):500-502.DOI:10.3760/cma.issn.0529-5807.2014.02.001.
[3]苏晓路,李小鸣.Aurora-A mt-P53和c-myc在大肠癌中的表达及意义[J].中国肿瘤临床,2014,41(3):170-174.DOI:10.3969/j.issn.1000-8179.20131265.
[4]Ferlay J,Shin HR,Bray F,et al.Estimates of worldwide burden of cancer in 2008.[J].Int J Cancer,2010,127(12):2893-2917.DOI:10.1002/ijc.25516.
[5]Lu XX,Yu JL,Ying LS,et al.Stepwise cumulation of RUNX3methylation mediated by Helicobacter pylori infection contributes to gastric carcinoma progression[J].Cancer,2012,118(22):5507-5517.DOI:10.1002/cncr.27604.
[6]Ito K.RUNX3 in oncogenic and anti-oncogenic signaling in gastrointestinal cancers[J].J Cell Biochem,2011,112(5):1243-1249.DOI:10.1002/jcb.23047.
[7]Voon D C,Wang H,Koo J K,et al.RUNX3 protects gastric epithelial cells against epithelial-mesenchymal transition-induced cellular plasticity and tumorigenicity[J].Stem Cells,2012,30(10):2088-2089.DOI:10.1002/stem.1183.
[8]Lee CW,Ito K,Ito Y.Role of RUNX3 in bone morphogenetic protein signaling in colorectal cancer[J].Cancer Res,2010;70(10):4243-4252.DOI:10.1158/0008-5472.
[9]Sun G,Zhang C,Feng M,et al.Methylation analysis of P16,SLIT2,SCARA5,and RUNX3 genes in hepatocellular carcinoma[J].Medicine,2017,10,96(41):e8279.DOI:10.1097/MD.0000000000008279.
[10]Kodach LL,Jacobs RJ,Heijmans J,et al.The role of EZH2 and DNA methylation in the silencing of the tumour suppressor RUNX3in colorectal cancer[J].Carcinogenesis,2010,31(9):1567-1575.DOI:10.1093/carcin/bgq147.
[11]何绍业,韩盛玺,薛任发.RUNX3基因甲基化及RUNX3蛋白表达在结直肠癌发生中的意义[J].世界华人消化杂志,2011,19,(17):1860-1863.DOI:10.3760/cma.j.issn.1007-631X.2012.08.016.
[12]Li L,Fu XS,Zhang W,et al.Wnt signaling pathway is activated in right colon serrated polyps correlating to specific molecular form ofβ-catenin[J].Hum Pathol,2013,44:1079-1088.DOI:10.1016/j.humpath.2012.09.013.
[13]王倩,张珊.Wnt经典信号通路在结直肠癌中的进展[J].医学综述,2017,23(5),907-909.DOI:1006-2084(2017)05-0907-05.
[14]Novellasdemunt L,Foglizzo V,et al.USP7 is a Tumor-Specific WNTactivator for APC-mutated colorectal cancer by mediatingβ-catenin deubiquitination[J].Cell Rep,2017,21(3):612-627.DOI:10.1016/j.celrep.2017.09.072.
[15]Miyawaki Y,Kawachi H,Ooi A,et al.Genomic copy-number alterations of MYC and FHIT genes are associated with survival in esophageal squamous-cell carcinoma[J].Cancer Sci,2012,103(8):1558-1566.DOI:10.1111/j.1349-7006.2012.02329.
[16]Pan S,Luo H,Li L.The C-myc mRNA and helicobacter pylori infection and the relationship between the programmed cell death in the with Gastric cancer in the patients with gastric cancer[J].Chinese Journal of Experimental Surgery,2013,30(11):2408-2410.DOI:10.3760/cma.j.issn.1001-9030.2013.11.059.
[17]Wright JB,Cole MD.Upergulation of C-myc in cis through a large chromatin lood linked to a cancer risk.associated single-nucleotide poly morphism in colorectal cancer cells[J].Molecular and Celluar Biology,2010,30(6):1411-1420.DOI:10.1128/MCB.01384-09.
[18]李超,许芝林,赵峥.K-ras基因与C-myc基因在大肠癌中的表达及相关性研究[J].哈尔滨医科大学学报,2009,43(6):572-575.DOI:10.3969/j.issn.1000-1905.2009.06.012.
[19]颜景旺,杜太平.Runx3基因Cp G岛甲基化在结肠癌病情及预后评估中的价值[J].临床著作,2017,4(20):287-290.DOI:10.3969/j.issn.1009-9905.2017.04.010.
[20]Kriegl L,Vieth M,Kirchner T,et al.Up-regulation of c-MYC and SIRT1 expression correlated with malignant transformation in the serrated route to colorectal cancer[J].Oncotarget,2012,3:1182-1193.DOI:10.18632/oncotarget.628.