Background:MLH1 promoter methylation analysis is recommended in screening for Lynch syndrome(LS)in patients with MLH1-deficient colorectal cancer(CRC).The study aims to identify specific methylation regions in the MLH1 promoter and to evaluate the clinicopathologic characteristics of and prognosis for patients with MLH1 methylation.Methods:A total of 580 CRC cases were included.The DNA mismatch repair(MMR)protein expression was assessed by using immunohistochemistry(IHC).The methylation status of the Regions A,B,C,D,and E in the MLH1 promoter was tested by using bisulfite sequencing PCR.The specificities of the five regions were calculated.Associations between MLH1 methylation and clinicopathologic characteristics were evaluated.Kaplan-Meier analyses for overall survival(OS)were carried out.Results:In 580 CRC cases,the specificities of the methylation test in Regions D and E were both 97.8%.In the MLH1-deficient CRCs,the frequencies of MLH1 methylation and BRAFV600E mutation were 52.6%and 14.6%,respectively;BRAFV600E mutation occurred in 27.7%of patients with MLH1-methylated CRC.In the MMR-deficient patients,compared with MLH1 unmethylation,MLH1 methylation was more common in patients who were aged≥50years,female,had no family history of LS-related tumors,and had tumors located at the right colon.In the MMR-deficient patients,the MLH1-methylated cases had lower OS rates than the unmethylated cases with a family history of LS-related tumors(P=0.047).Conclusions:Regions D and E in the MLH1 promoter are recommended for determining the MLH1 methylation status in screening for LS in MLH1-deficient CRC.In MMR-deficient patients,the MLH1-methylated cases had a worse OS than the unmethylated cases with a family history of LS-related cancer.
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。
