痰液、血液和纤维支气管镜活检组织中P16INK4a基因甲基化与临床肺癌诊断的关系

摘要

Objective:To investigate the relationship between the methylation of P16INK4a gene in blood, sputum, and fiberoptic bronchoscopy biopsy and the clinical diagnosis of lung cancer. Methods: Methylation - specific PCR (MSP) had been used to test the P16INK4a mathlation in blood, sputum and fiber bronchoscopic biopsy samples from 40 cases of lung cancer and 45 patients diagnosed with generally respiratory diseases. The diagnostic feature of lung cancer had been compared between two goups of single tissue specimen and joint detection of multiple source tissue specimen from the cases of lung cancer. Results: The positive rate of MSP in blood, sputum, and fiberoptic bronchoscopy biopsy samples from the patients with lung cancer were 54. 54% ( 18/33 ) ,65. 00% ( 13/20 )and 71. 43% ( 10/ 14 ), and the patients with ordinary respiratory disease were 18. 18% ( 6/33 ),23. 08% (3/13 )and 23. 53% ( 4/17 ) respectively. The difference between them was significant ( P<0. 05 ). The positive rate of the multiple source tissue specimen from lung cancer joint detection was 85. 00% , the difference compared with the former two was signifcant ( P < 0. 05 ) . The accuracy, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio were 84. 71 % , 82. 93% , 86. 36% , 5. 46, and 0. 18 respectively. Conclusion: It was higher significantly that the positive rate of P16INK4a methylation in sputum, blood and fiberoptic bronchoscopy biopsy samples from the patients with lung cancer compared with one of the patients with ordinary disease( P < 0. 05 ). It suggested that the measure of P16INK4a MSP should be in favour of lung cancer diagnosis when a patient be suspicious of lung cancer. The diagnosis efficiency of lung cancer will be improved when the joint detection of multiple source of tissue sample from the same patient is carried out.%目的 探讨血液、痰液和纤维支气管镜活检组织中的P16INK4a基因甲基化与临床肺癌诊断的关系.方法 运用甲基化特异度聚合酶链技术(methylation-specific PCR,MSP)检测40例临床诊断肺癌患者和45例一般呼吸道疾病患者血液、纤维支气管镜活检组织和痰液标本中P16INK4a的甲基化状况.比较单一组织来源标本检测和多种组织来源标本联合检测诊断肺癌的诊断特性.结果 肺癌患者单一血液、痰液和纤维支气管镜活检组织来源标本中甲基化阳性率分别为54.54%(18/33)、65.00%(13/20)和71.43%(10/14);一般呼吸道疾病患者的单一血液、痰液和纤维支气管镜活检组织来源标本中的甲基化阳性率分别为18.18%(6/33)、23.08%(3/13)和23.53%(4/17);两者比较差异显著(P<0.05);肺癌患者多种组织来源标本联合检测甲基化阳性率为85.00%,和前二者比较差异有显著性(P<0.05).联合检测诊断试验的准确率为84.71%,阳性预测值82.93%,阴性预测值86.36%,阳性似然比为5.46,阴性似然比0.18.结论 肺癌患者痰液、血液和纤维支气管镜活检组织中P16INK4a基因甲基化有助于肺癌诊断,对同一患者获取多种组织来源标本联合检测,可提高检测阳性率.