外周血DNA TUSC4基因缺失在大肠癌分子筛查及早期诊断中的应用  

Significance of detection of TUSC4 gene deletion in peripheral blood DNA for molecular screening and diagnosis of colorectal carcinoma

作　　者：裴凤华[1] 赵晶[1] 杜雅菊[1] 程艳秋[2] 王晓芬[2] 陈晶[1] 张会涛[1] 刘冰熔[1] 高善玲[1] 

机构地区：[1]哈尔滨医科大学附属第二医院消化内科,黑龙江省哈尔滨市150086 [2]哈尔滨医科大学附属第二医院消化内镜中心,黑龙江省哈尔滨市150086

出　　处：《世界华人消化杂志》2010年第31期3320-3326,共7页World Chinese Journal of Digestology

基　　金：黑龙江省卫生厅科研课题基金资助项目;No.2007-303~~

摘　　要：目的:探讨外周血DNA中肿瘤抑制候选基因4(tumor suppressor candidate4,TUSC4)缺失在大肠癌的筛查与早期诊断中的意义.方法:采集外周静脉血标本238例,分为结肠镜正常组(117例),腺瘤型息肉组(38例)和大肠癌组(83例),应用PCR法检测TUSC4基因表达及缺失情况.同时检测各组血浆CEA、CA19-9水平.结果:结肠镜正常组TUSC4阴性率14.5%,腺瘤型息肉组阴性率44.7%,大肠癌组阴性率77.1%,3组之间均有统计学差异(P=0.000).TUSC4阴性在诊断腺瘤型息肉的敏感度为44.7%(95%CI28.9%-60.5%),特异度85.5%(95%CI79.1%-91.9%),PPV为50.0%(95%CI33.2%-66.8%),NPV为82.6%(95%CI75.8%-89.4%).TUSC4阴性在诊断大肠癌的敏感度为77.1%(95%CI68.1%-86.1%),特异度为85.5%(95%CI79.1%-91.9%),PPV为79.0%(95%CI70.1%-87.9%),NPV为84.0%(95%CI77.4%-90.6%).TUSC4基因缺失与大肠癌发生部位、分化程度及Dukes分期无关.TUSC4阴性在诊断大肠癌时与CEA、CA19-9相比较,其特异度和PPV无统计学差异(P>0.05),其敏感度和NPV明显高于CEA和CA19-9(P=0.000).结论:大肠癌患者外周血DNA中TUSC4基因出现明显缺失,在诊断大肠癌时其敏感度明显高于CEA和CA19-9,在大肠癌的分子筛查和分子诊断中具有一定应用价值.AIM：To detect tumor suppressor candidate 4（TUSC4） gene deletion in peripheral blood DNA and to evaluate its significance for molecular screening and diagnosis of colorectal carcinoma.METHODS：Polymerase chain reaction was used to detect TUSC4 gene deletion in peripheral blood DNA samples from 238 subjects,including 117 subjects with normal colonoscopic findings,38 patients with adenoma polyp,and 83 patients with colorectal carcinoma.RESULTS：TUSC4 gene deletion was detected in peripheral blood DNA samples in 14.5%,44.7% and 77.1% of normal subjects,adenoma polyp patients and colorectal carcinoma patients,respectively.The percentage of subjects carrying TUSC4 gene deletion differed significantly among the three groups of subjects（all P = 0.000）.The sensitivity,specificity,positive predictive value（PPV） and negative predictive value（NPV） of detection of TUSC4 gene deletion in peripheral blood DNA for diagnosis of adenoma polyp were 44.7%（95%CI 28.9%-60.5%）,85.5%（95%CI 79.1%-91.9%）,50.0%（95%CI 33.2%-66.8%） and 82.6%（95%CI 75.8%-89.4%）,respectively,while the corresponding values for diagnosis of colorectal carcinoma were 77.1%（95%CI 68.1%-86.1%）,85.5%（95%CI 79.1%-91.9%）,79.0%（95%CI 70.1%-87.9%） and 84.0%（95%CI 77.4%-90.6%）.TUSC4 gene deletion in peripheral blood DNA was not significantly related to tumor site,differentiation degree and Dukes stage.Compared with detection of CEA and CA19-9,the specifi city and PPV of detection of TUSC4 gene deletion for diagnosis of colorectal carcinoma were not significantly different（all P〈0.05）.However,the sensitivity and NPV of detection of TUSC4 gene deletion for diagnosis of colorectal carcinoma were significantly higher than those of detection of CEA and CA19-9（all P = 0.000）.CONCLUSION：USC4 gene deletion in peripheral blood DNA can be detected in patients with colorectal carcinoma.The sensitivity of detection of TUSC4 gene deletion for diagnosis of colorectal carcinoma is significantly higher than that of detectio

关 键 词：肿瘤抑制候选基因4 抑癌基因 大肠癌 分子筛查 分子诊断 

分 类 号：R735.3[医药卫生—肿瘤]