摘要
目的:对疑诊肺癌患者支气管肺泡灌洗液(BALF)中SHOX2、RASSF1A基因甲基化分析,评估两指标联合检测区分肺癌与肺良性疾病的诊断效能及联合细胞学使用对肺癌的诊断价值。方法:收集276例肺部疾病患者(肺癌组131例,肺部良性疾病组145例)的BALF样本,应用PCR法检测BALF中SHOX2和RASSF1A基因甲基化,并将检测结果和Sanger测序法结果比较。结果:PCR和Sanger测序法一致性分析显示两种方法在检测SHOX2和RASSF1A基因甲基化具有良好的一致性(Kappa=0.978,95%CI=0.954~1.000)。SHOX2和RASSF1A基因甲基化联合检测在肺癌组的诊断灵敏度为0.840,高于良性疾病组(0.193)(P<0.001);肺癌组BALF中SHOX2、RASSF1A基因甲基化联合检测阳性率在小细胞肺癌和肺鳞癌中分别是100%和90.9%,高于肺腺癌(66.0%);SHOX2和RASSF1A基因甲基化联合检测阳性率在晚期肺癌高达89.3%,明显高于早期肺癌阳性检出率。ROC曲线分析显示当SHOX2、RASSF1A基因甲基化、细胞学三指标联合使用时进一步将诊断灵敏度提高至0.931。结论:对BALF中SHOX2、RASSF1A基因甲基化PCR检测在肺癌诊断中有良好的灵敏度;SHOX2、RASSF1A甲基化PCR检测与细胞学联合使用可显著提高肺癌诊断灵敏度,是肺癌病理学诊断的有效补充工具。
Aim:To analyze the methylation of SHOX2 and RASSF1A genes in bronchoalveolar lavage fluid(BALF)of patients with suspected lung cancer,and to evaluate the diagnostic efficacy of combination of two indicators to distinguish lung cancer from benign lung disease and the diagnostic value of combined cytology for lung cancer.Methods:The BALF samples of 276 patients with lung diseases(131 patients with lung cancer,145 patients with benign lung lesion)were collected and the methylation of SHOX2 and RASSF1A genes in BALF were detected by PCR.The results were compared with the results of Sanger sequencing.Results:Consistency analysis of PCR and Sanger sequencing showed that the two methods were in good agreement for detecting SHOX2 and RASSF1A gene methylation(Kappa=0.978,95%CI=0.954-1.000).The combined sensitivity of SHOX2 and RASSF1A gene methylation in the lung cancer group was 0.840,which was significantly higher than that in the control group(0.193)(P<0.001).The positive rate of combined detection of SHOX2 and RASSF1A gena methylation in BALF was 100%and 90.9%in small cell lung cancer and squamous cell lung cancer respectively,higher than that(66.0%)in lung adenocarcinoma;The positive rate of combined detection of SHOX2 and RASSF1A gena methylation was 89.3%in advanced lung cancer,higher than early lung cancer.ROC curve analysis showed that when the SHOX2,RASSF1A gene methylation and cytology were used in combination,the diagnostic sensitivity was further increased to 0.931.Conclusion:The methylation analysis of SHOX2 and RASSF1A genes in BALF by PCR has good sensitivity and specificity in the diagnosis of lung cancer;SHOX2,RASSF1A methylation analysis by PCR combined with cytology can significantly improve the sensitivity of lung cancer diagnosis,and is an effective supplement for pathological diagnosis of lung cancer.
作者
陈瑞英
刘雅
孙婷
刘峰辉
马小花
CHEN Ruiying;LIU Ya;SUN Ting;LIU Fenghui;MA Xiaohua(Department of Respiration and Sleep Medicine,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052;Department of Respiration,the Fifth Affiliated Hospital,Zhengzhou University,Zhengzhou 450052)
出处
《郑州大学学报（医学版）》
CAS
北大核心
2019年第5期732-736,共5页
Journal of Zhengzhou University(Medical Sciences)
基金
河南省科技攻关项目(172102310087)
