FBN1、FBN2基因甲基化与食管癌的相关性研究
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摘要
目的:研究食管癌组织原纤蛋白-1(Fibrillin-1,FBN1)与原纤蛋白-2(Fibrillin-2,FBN2)基因启动子区的甲基化状态,进一步探讨FBN1、FBN2基因甲基化与食管癌的相关性,为研究肿瘤的发生发展等提供一定的理论基础。方法:采用甲基化特异性PCR(methylation special PCR,MSP)检测方法,检测95例食管癌组织标本、癌旁组织标本的FBN1、FBN2基因启动子区甲基化状态。采用Western blot检测肿瘤组织的蛋白含量,并分析蛋白表达与基因的相关性。结果:食管癌组织和癌旁组织中FBN1基因甲基化发生率分别为86.3%(82/95)和5.3%(5/95);FBN2基因甲基化发生率分别为82.1%(78/95)和8.4%(8/95),差异均具有统计学意义(P<0.001)。根据分化程度、TNM分期、性别等对患者进行分组,各组之间均无明显差异(P>0.05)。Western blot检测结果提示基因甲基化明显影响蛋白表达,使蛋白表达量明显减少。结论 :FBN1、FBN2基因甲基化与食管癌的发生发展具有十分密切的关系,该基因可以作为一种潜在的抑癌基因,对研究食管癌的发病机制及治疗提供潜在的理论基础。
Objective: This paper tested the Fibrillin-1( FBN1) and Fibrillin-2( FBN2) gene promoter methylation status in tumor tissue of esophageal cancer patients,to further explore the relationship between the methylation of these genes and esophageal cancer,to provide a theoretical basis for the study of tumor development. Methods: Methylation specific PCR( MSP) detection method was used to detect the methylation status of FBN1 and FBN2 gene promoter in 95 cases of esophageal cancer tissues and adjacent tissues specimens. Results: The methylation rate of FBN1 gene in esophageal cancer tissues and adjacent tissues were 86. 3 %( 82/95) and 5. 3 %( 5/95). The rates of FBN2 gene methylation were 82. 1 %( 78/95) and 8. 4 %( 8/95),the difference was statistically significant( P < 0. 001).And the patients were divided into groups according to the degree of differentiation,TNM stage,gender and so on,there was no significant difference between the groups( P > 0. 05). Conclusion:There is a very close relationship between the methylation of FBN1/FBN2 gene and esophageal cancer. The gene can be used as a potential tumor suppressor gene,and this study may provide a theoretical basis for the potential pathogenesis and treatment of esophageal cancer.
Objective: This paper tested the Fibrillin-1( FBN1) and Fibrillin-2( FBN2) gene promoter methylation status in tumor tissue of esophageal cancer patients,to further explore the relationship between the methylation of these genes and esophageal cancer,to provide a theoretical basis for the study of tumor development. Methods: Methylation specific PCR( MSP) detection method was used to detect the methylation status of FBN1 and FBN2 gene promoter in 95 cases of esophageal cancer tissues and adjacent tissues specimens. Results: The methylation rate of FBN1 gene in esophageal cancer tissues and adjacent tissues were 86. 3 %( 82/95) and 5. 3 %( 5/95). The rates of FBN2 gene methylation were 82. 1 %( 78/95) and 8. 4 %( 8/95),the difference was statistically significant( P < 0. 001).And the patients were divided into groups according to the degree of differentiation,TNM stage,gender and so on,there was no significant difference between the groups( P > 0. 05). Conclusion:There is a very close relationship between the methylation of FBN1/FBN2 gene and esophageal cancer. The gene can be used as a potential tumor suppressor gene,and this study may provide a theoretical basis for the potential pathogenesis and treatment of esophageal cancer.
引文
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[2]Kulis M,Esteller M.DNA methylation and cancer[J].Advances in Genetics,2010,70(22):27.
[3]Levenson VV.DNA methylation biomarkers of cancer:Moving toward clinical application[J].Pharmacogenomics,2016,5(5):699-707.
[4]Wittenberger T,Sleigh S,Reisel D,et al.DNA methylation markers for early detection of women's cancer:Promise and challenges[J].Epigenomics,2017,6(3):311.
[5]Chen H.Study on the relationship between FBN2 gene and lung cancer cell[J].Journal of Chongqing Medical University,2007,32(11):1175-1177.[陈虹.FBN2基因与肺癌细胞关系的初步探讨[J].重庆医科大学学报,2007,32(11):1175-1177.]
[6]Bakulski KM,Dolinoy DC,Sartor MA,et al.Genome-wide DNA methylation differences between late-onset Alzheimer's disease and cognitively normal controls in human frontal cortex[J].Journal of Alzheimers Disease Jad,2017,29(3):571-588.
[7]Kaut O,Sharma A,Schmitt I,et al.DNA methylation of imprinted loci of autosomal chromosomes and IGF2 is not affected in Parkinson's disease patients'peripheral blood mononuclear cells[J].Neurological Research,2017,39(3):1-4.
[8]Li WH,Zhang H,Guo Q,et al.Detection of SNCA and FBN1 methylation in the stool as a biomarker for colorectal cancer[J].Disease Markers,2015,15(6):570-575.
[9]Guo Q,Song Y,Zhang H,et al.Detection of hypermethylated fibrillin-1 in the stool samples of colorectal cancer patients[J].Medical Oncology,2013,30(4):1-5.
[10]Pehlivan S,Artac M,Sever T,et al.Gene methylation of SFRP2,p16,DAPK1,HIC1,and MGMT and KRAS mutations in sporadic colorectal cancer[J].Cancer Genetics&Cytogenetics,2010,201(2):128-132.
[11]Ida S,Bryden G,Lin DNC,et al.Orbital migration of neptune and orbital distribution of trans-neptunian objects[J].Astrophysical Journal,2008,534(1):428.