肺癌患者支气管肺泡灌洗液中DAPL1和MLH1基因甲基化水平检测及其临床意义研究  

Detection and Clinical Significance of DAPL1 and MLH1 Gene Methylation in Bronchoalveolar Lavage Fluid of Lung Cancer Patients

作　　者：罗世龙 李志强[2] 李翔 LUO Shilong;LI Zhiqiang;LI Xiang(Department of Medical Oncology,the Second People’s Hospital of Mengcheng County,Anhui Mengcheng 233500,China;Department of Nutrition,the Second People’s Hospital of Mengcheng County,Anhui Mengcheng 233500,China)

机构地区：[1]蒙城县第二人民医院肿瘤内科,安徽蒙城233500 [2]蒙城县第二人民医院营养科,安徽蒙城233500

出　　处：《现代检验医学杂志》2024年第5期125-129,共5页Journal of Modern Laboratory Medicine

摘　　要：目的检测肺癌患者支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中凋亡相关蛋白激酶样蛋白1(death-associated protein kinase like 1,DAPL1)和错配修复基因(Mut L homologue l,MLH1)甲基化水平,进一步研究基因甲基化对早期肺癌的诊断价值及其与临床病理特征的关系。方法回顾性选取2022年1月~2024年1月蒙城县第二人民医院收治的疑似早期肺癌患者142例,根据最终病理学结果分为肺癌组(n=82)和肺部良性病变组(n=60)。采用实时定量聚合酶链反应(qRT-PCR)法检测两组BALF样本中DAPL1和MLH1甲基化水平;分析DAPL1和MLH1甲基化对早期肺癌的临床诊断价值及其与肺癌患者临床病理特征的关系。结果肺癌组患者BALF中DAPL1和MLH1基因甲基化水平分别为53.66%(44/82),56.10%(46/82),明显高于良性病变组的11.67%(7/60)和18.33%(11/60),差异具有统计学意义(χ^(2)=56.544,20.565,均P<0.05)。DAPL1和MLH1基因甲基化诊断早期肺癌的敏感度分别为53.66%(44/82)和56.10%(46/82),特异度分别为88.33%(53/60)和81.67%(49/60),准确度分别为68.31%(97/142)和66.90%(95/142);DAPL1甲基化联合MLH1甲基化诊断早期肺癌的敏感度和准确度分别为86.59%(71/82),85.92%(122/142),均高于单一指标(Z=24.411,16.450,均P<0.05)。肺癌患者BALF中DAPL1和MLH1基因甲基化水平与临床分期、吸烟史及淋巴结转移密切相关(χ^(2)=5.493,13.083;8.167,6.946;9.303,4.523,均P<0.05)。Spearman相关性显示,DAPL1和MLH1基因甲基化与肺癌患者临床分期、吸烟史及淋巴结转移均呈正相关(r=0.523,0.602;0.548,0.498;0.630,0.524,均P<0.05)。结论BALF中DAPL1和MLH1基因甲基化检测对于早期肺癌具有较高的临床诊断价值,且两者基因甲基化水平与肺癌患者病情进展及吸烟史有关。Objective To detect the expression of death-associated protein kinase like 1(DAPL1)and mismatch repair gene(Mut L homologue l,MLH1)methylation level in bronchoalveolar lavage fluid(BALF)of patients with lung cancer,and further investigate the diagnostic value of gene methylation in early lung cancer and its relationship with clinicopathological features.Methods A total of 142 patients with suspected early stage lung cancer admitted the Second People’s Hospital of Mengcheng County from January 2022 to January 2024 were retrospectively selected and divided into lung cancer group(n=82)and lung benign lesion group(n=60)according to the final pathological results.Quantitative real time polymerase chain reaction(qRTPCR)was used to detect the methylation levels of DAPL1 and MLH1 in BALF samples.The clinical diagnostic value of DAPL1 and MLH1 methylation in early stage lung cancer and its relationship with clinicopathological features of lung cancer patients were analyzed.Results The methylation levels of DAPL1 and MLH1 gene in BALF in lung cancer group were 53.66%(44/82)and 56.10%(46/82),respectively,which were significantly higher than those in benign disease group[11.67%(7/60)and 18.33%(11/60)],and the difference was statistically significant(χ^(2)=56.544,20.565,all P<0.05).The sensitivity of DAPL1 and MLH1 gene methylation in the diagnosis of early lung cancer was 53.66%(44/82)and 56.10%(46/82),the specificity was 88.33%(53/60)and 81.67%(49/60),and the accuracy were 68.31%(97/142)and 66.90%(95/142),respectively.The sensitivity and accuracy of DAPL1 methylation combined with MLH1 methylation in the diagnosis of early lung cancer was 86.59%(71/82),and 85.92%(122/142),respectively,both of which were higher than that of a single index(Z=24.411,16.450,all P<0.05).The methylation levels of DAPL1 and MLH1 genes in BALF of lung cancer patients were closely correlated with clinical stage,smoking history and lymph node metastasis(χ^(2)=5.493,13.083;8.167,6.946;9.303,4.523,all P<0.05).Spearman correlation showed that DAPL1

关 键 词：肺癌 支气管肺泡灌洗液 凋亡相关蛋白激酶样蛋白1 错配修复基因 基因甲基化 

分 类 号：R734.2[医药卫生—肿瘤] R730.43[医药卫生—临床医学]