驱动基因阳性肺癌外周血EGFR甲基化及临床意义  

EGFR Methylation in Peripheral Blood of Driver Gene-Positive Lung Cancer and its Clinical Correlation.

作　　者：刘东 李真 王保庆 王自全 王丙武 李庆妍 LIU Dong;LI Zhen;WANG Baoqing(Department of Medical Oncology,Second Affiliated Hospital of Xuzhou Medical University,Department of Pharmacy,Second Affiliated Hospital of Xuzhou Medical University,Jiangsu 221000,China)

机构地区：[1]徐州医科大学第二附属医院肿瘤内科,221000 [2]徐州医科大学第二附属医院药学部,221000

出　　处：《医学研究杂志》2024年第1期151-156,共6页Journal of Medical Research

基　　金：江苏省药学会-恒瑞医院药学基金资助项目(H202036)。

摘　　要：目的探讨EGFR驱动基因阳性肺癌患者外周血中EGFR甲基化水平与临床意义。方法运用基质辅助激光电离飞行质谱(matrix-assisted laser desorption/ionisation,time-of-flight mass spectrometry,MALDI-TOF MS)法检测32例EGFR驱动基因阳性(EGFR 19del、21 L858R)肺腺癌患者和24例正常对照组外周血中EGFR基因CpG岛甲基化水平,筛选肺癌发生差异性甲基化CpG位点,并分析其与临床病理特征、EGFR突变亚型的相关性。结果EGFR在EGFR驱动基因阳性肺癌组中甲基化水平普遍低于正常对照组,其中EGFR#29 CpG_2,EGFR#30 CpG_8.9.10.11、CpG_25、CpG_40.41.42在肺癌组中甲基化率(25.7%±2.1%、4.6%±0.4%、2.8%±0.7%、4.4%±0.4%)低于正常对照组(36.5%±4.6%、6.0%±0.6%、4.8%±0.9%、7.1%±0.4%),差异有统计学意义(P<0.05)。EGFR甲基化与肺癌患者年龄、分化程度、发病位置、TNM分期均无相关性(P>0.05)。EGFR#30 CpG_25在女性肺癌患者中较男性患者呈现较低的甲基化水平,差异有统计学意义(P<0.05)。EGFR#30 CpG_25在吸烟组肺癌患者中较不吸烟患者呈高甲基化状态,差异有统计学意义(P<0.05)。而EGFR#30 CpG_8.9.10.11在淋巴结转移组中的甲基化水平要低于无淋巴结转移组,差异有统计学意义(P<0.05)。EGFR在EGFR 19del和21 L858R突变亚型中的甲基化比较,差异无统计学意义(P>0.05)。结论EGFR甲基化可能与EGFR驱动基因阳性肺癌的发生、发展以及患者的性别、吸烟史有关,并有可能作为肺癌诊断和预后预测的分子标志物。Objective To explore the methylation status of EGFR promoter region in peripheral blood of EGFR driver gene-positive lung adenocarcinoma patients and its clinical significance.Methods The methylation of EGFR promoter region in peripheral blood DNA of 32 EGFR driver gene-positive lung adenocarcinoma patients and 24healthy controls were detected by(matrix-assisted laser desorption/ionisation,time-of-flight mass spectrometry,MALDI-TOF MS)technique to screen the differential methylation of CpG sites with lung cancer and analyze its correlation with clinicopathological characteristics and EGFR mutant subtype.Results The methylation levels of EGFR were significantly lower in the lung cancer group than in the normal control,EGFR#29 CpG_2,EGFR#30 CpG_8.9.10.11,CpG_25,CpG_40.41.42methylation of lung cancer group(25.7%±2.1%,4.6%±0.4%,2.8%±0.7%,4.40±0.4%)were lower than the normal control(36.5%±4.6%,6.0%±0.6%,4.8%±0.9%,7.1%±0.4%),the difference was statistically significant(P<0.05).No significant differences in the methylation levels within EGFR CpGs were associated with age,cancer differentiation,disease location,TNM stage with lung cancer(P>0.05).The methylation level of EGFR#30 CpG_25 in the female group was significantly lower than that in the male group(P<0.05),and the methylation level of EGFR#30 CpG_25 in the smoking group was higher than that in the non-smoking group(P<0.05),the methylation level of EGFR#30 CpG_8.9.10.11 in the lymph node metastasis group was significantly lower than that in the non-lymph node metastasis(P<0.01).There was no significant difference in methylation of EGFR between EGFR 19del and 21 L858R mutant subtypes.Conclusion Our findings suggest that EGFR methylation may be associated with the occurrence,development,gender,and smoking history of patients with EGFR driving gene-positive lung cancer,which may serve as a biomarker for the diagnosis and prognosis prediction of lung cancer.

关 键 词：肺肿瘤 外周血 EGFR 甲基化 MALDI-TOF MS 

分 类 号：R734.2[医药卫生—肿瘤]