张毅敏,王明丽,吴 杰.肺泡灌洗液中SHOX2和RASSF1A基因[J].肿瘤学杂志,2016,22(12):1032-1036.
肺泡灌洗液中SHOX2和RASSF1A基因
Combined Detection of SHOX2 and RASSF1A Gene Methylation in Bronchoalveolar Lavage Fluid for Diagnosis of Lung Cancer
投稿时间:2016-09-17  
DOI:10.11735/j.issn.1671-170X.2016.12.B010
中文关键词:  SHOX2  RASSF1A  基因甲基化  肺泡灌洗液  肺肿瘤
英文关键词:SHOX2  RASSF1A  gene methylation  bronchoalveolar lavage fluid  lung neoplasms
基金项目:浙江省医药卫生科技项目(2014KYB043;2016KYB034)
作者单位
张毅敏 浙江省肿瘤医院 
王明丽 浙江省肿瘤医院 
吴 杰 浙江省肿瘤医院 
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中文摘要:
      摘 要:[目的] 评估肺泡灌洗液(BALF)中SHOX2和RASSF1A基因甲基化联合检测(任意阳性)在肺癌诊断中的临床价值。[方法]收集经病理确诊的580例患者,其中肺癌261例,良性肺部疾病293例,非肺部的恶性肿瘤26例。将良性肺部疾病和非肺部的恶性肿瘤患者共319例作为对照组。对全部580例患者的BLAF样本,采用实时荧光PCR(RT-PCR)与测序法检测BALF中SHOX2和RASSF1A两种基因甲基化情况,比较两种检测方法的一致性。以病理诊断为金标准,对277例具有细胞学结果的患者(肺癌组130例,对照组147例),比较采用RT-PCR法SHOX2和RASSF1A基因甲基化检测与细胞学检测对肺癌诊断的敏感性和特异性。[结果] RT-PCR法与测序法两种方法检测580例患者BLAF样本SHOX2基因和RASSF1A基因甲基化结果的一致率分别是97.5%和98.0%。580例BLAF样本采用RT-PCR法检测SHOX2和RASSF1A基因甲基化任意阳性对肺癌诊断的敏感性和特异性分别是74.3%和87.1%。在277例有细胞学结果的患者中,RT-PCR法SHOX2和RASSF1A基因甲基化检测任意阳性对肺癌诊断的敏感性和特异性分别为83.2%和92.5%,与细胞学检测(44.6%和98.6%)相比,敏感性显著提高,但特异性有所降低,差异均有统计学意义(P<0.01,P<0.05)。基因甲基化联合检测(任意阳性)阳性率在细胞学发现癌细胞组为98.2%(57/58),结果未明组为100.0%(35/35),未发现癌细胞组为37.8%(14/37)。[结论] 采用RT-PCR法进行BALF中SHOX2和RASSF1A基因甲基化联合检测,可以作为肺癌细胞学检查的补充,特别是在细胞学检测结果未明或阴性时。
英文摘要:
      Abstract:[Objective] To evaluate the application of combined detection of SHOX2 and RASSF1A gene methylation in bronchoalveolar lavage fluid(BALF) for diagnosis of lung cancer. [Methods] BLAF samples and the pathological data were collected from 261 patients with lung cancer and 319 controls. The methylation statues of SHOX2 and RASSF1A genes in BALF were detected by quantified real-time PCR(RT-PCR) and sequencing,and the consistency of two methods was analyzed. The sensitivity and specificity of either positive SHOX2 or RASSF1A methylation for diagnosis of lung cancer were compared with cytological examination in 277 patients with cytological results (130 cases in lung cancer group,147 controls) .[Results] The consistency rates of SHOX2 and RASSF1A gene methylation detected by RT-PCR and sequencing were 97.5% and 98.0%,respectively. The sensitivity and specificity of combined positive SHOX2 and RASSF1A methylation for diagnosis of lung cancer in 580 BALF samples detected by RT-PCR were 74.3% and 87.1%,respectively. In 277 cases with cytological results,the sensitivity of combined detection of SHOX2 and RASSF1A methylation for diagnosis of lung cancer detected by RT-PCR was 83.2%,higher than that in cytological detection(44.6%,P<0.01); and the specificity in gene methylation(92.5%) was lower than that in cytological detection(98.6%,P<0.05). The positive rate of combined SHOX2 and RASSF1A gene methylation was 98.2%(57/58)in cytology positive group,100.0%(35/35) in cytology undetermined group,and 37.8%(14/37)in cytology negative group. [Conclusion] Combination detection of methylation of SHOX2 and RASSF1A genes in BALF by RT-PCR may be used as a supplement to cytology for diagnosis of lung cancer,especially in patients with undetermined or negative cytology.
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