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

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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. Objective: To investigate the significance of tumor suppressor candidate 4 (TUSC4) deletion in the screening and early diagnosis of colorectal cancer.Methods: 238 peripheral blood samples were collected and divided into normal colonoscopy group 117 cases), adenomatous polyp group (38 cases) and colorectal carcinoma group (83 cases). The expression and deletion of TUSC4 gene were detected by PCR.At the same time, the levels of plasma CEA and CA19-9 in each group were detected.Results: The negative rate of TUSC4 was 14.5% in group A, 44.7% in adenomatous polyps and 77.1% in large intestine carcinoma (P = 0.000) .TUSC4 was negative in diagnosing adenoma polyps (95% CI 28.9% -60.5%), specificity 85.5% (95% CI 79.1% -91.9%), PPV 50.0% (95% CI 33.2% -66.8%), and NPV was 82.6% (95% CI75.8% -89.4%). The sensitivity of TUSC4-negative in the diagnosis of colorectal cancer was 77.1% (95% CI68.1% -86.1%) and the specificity was 85.5% (95% CI79.1% -91.9%), PPV was 79.0% (95% CI70.1% -87.9%) and NPV was 84.0% (95% CI77.4% -90.6%). The location of TUSC4 gene deletion, Staging unrelated.TUSC4 negative in the diagnosis of colorectal cancer with CEA, CA19-9 compared to its specificity and PPV no statistics (P> 0.05), and the sensitivity and NPV of CEA and CA19-9 were significantly higher than those of CEA and CA19-9 (P = 0.000) .Conclusion: The TUSC4 gene in peripheral blood of patients with colorectal cancer is obviously missing and its sensitivity is obvious in the diagnosis of colorectal cancer Higher than CEA and CA19-9, in molecular screening and molecular diagnosis of colorectal cancer has a certain value.
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