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目的探讨支气管灌洗液抑癌基因过甲基化对肺癌诊断的应用价值。方法选取北京市结核病胸部肿瘤研究所收治怀疑肺癌患者78例,包括肺癌51例和良性病变患者27例,从支气管灌洗液上清和细胞提取DNA,对上清游离DNA进行定量分析,并采用NMSP完成对支气管灌洗液上清和细胞的过甲基化分析,所选择的靶基因包括p16,MGMT以及RASSF1A基因。将NMSP结果与临床诊断比较,计算敏感性和特异性。结果中心型肺癌、周围型肺癌和肺部良性病变支气管灌洗液上清游离DNA含量没有显著差异。支气管灌洗液细胞抑癌基因过甲基化诊断中心型肺癌的敏感性和特异性分别为85.2%和81.5%,诊断周围型肺癌的敏感性和特异性分别为54.2%和81.5%。支气管灌洗液上清和细胞抑癌基因过甲基化诊断中心型肺癌的敏感性和特异性为88.9%和70.4%,诊断周围型肺癌的敏感性和特异性为75.0%和70.4%。结论支气管灌洗液抑癌基因的过甲基化可为肺癌诊断提供帮助。
Objective To investigate the value of tumor suppressor gene hypermethylation in bronchoalveolar lavage fluid in the diagnosis of lung cancer. Methods Totally 78 patients with lung cancer, including 51 lung cancer patients and 27 patients with benign disease, were enrolled from the Institute of Tuberculosis and Thoracic Tumors of Beijing. DNA was extracted from the supernatant and cells of bronchoalveolar lavage fluid and quantitatively analyzed for the free DNA of supernatant. NMSP Complete over-methylation analysis of bronchoalveolar lavage fluid and cells, selected target genes include p16, MGMT and RASSF1A genes. The NMSP results were compared with the clinical diagnosis to calculate the sensitivity and specificity. Results There was no significant difference in the content of free DNA in the bronchial lavage fluid of central lung cancer, peripheral lung cancer and benign lung disease. The sensitivity and specificity of bronchial lavage fluid tumor suppressor gene hypermethylation in the diagnosis of central lung cancer were 85.2% and 81.5%, respectively. The sensitivity and specificity in diagnosing peripheral lung cancer were 54.2% and 81.5% respectively. The sensitivity and specificity of bronchial fluid supernatant and hypermethylation of tumor suppressor gene in central bronchial carcinoma were 88.9% and 70.4%, respectively. The sensitivity and specificity of bronchial lavage fluid and tumor suppressor gene in diagnosing peripheral lung cancer were 75.0% and 70.4%, respectively. Conclusion The hypermethylation of the tumor suppressor gene in bronchoalveolar lavage fluid may be helpful in the diagnosis of lung cancer.