非小细胞肺癌组织中DNMT1表达和hMLH1、hMSH2甲基化状态的变化及意义

摘要

目的 探讨非小细胞肺癌(NSCLC)癌及癌旁组织中DNMT1表达和hMLH1、hMSH2基因甲基化状态的变化及意义.方法 通过实时荧光定量PCR法检测52例肺癌及癌旁组织中DNMT1表达,同时用甲基化特异性PCR(MSP)法检测hMLH1、hMSH2基因启动子区甲基化状态.DNMT1表达与hMLH1、hMSH2启动子区甲基化水平相关性用Spearman相关分析.结果 52例NSCLC患者癌及癌旁组织中DNMT1 mRNA相对表达量分别为3.1623±0.5125、2.8731±0.3706,P<0.01;癌及癌旁组织中hMLH1基因启动子区甲基化阳性率分别为53.8%(28/52)、32.7%(17/52),差异有统计学意义(χ2=4.740,P<0.05);癌及癌旁组织中hMSH2基因启动子区甲基化阳性率分别为57.7%(30/52)、34.6%(18/52),差异有统计学意义(χ2=5.571,P<0.05).hMLH1、hMSH2启动子区甲基化水平与患者性别、年龄、肿瘤大小、病理学类型、淋巴结转移、侵犯周围组织等无关(P均>0.05).DNMT1表达与hMLH1、hMSH2启动子区甲基化水平呈显著正相关(r分别为0.479、0.528,P均<0.05).结论 NSCLC癌组织中DNMT1呈高表达,DNMT1表达与hMLH1、hMSH2基因启动子区甲基化水平呈正相关性;三者表达与NSCLC患者临床病理特征无关.%Objective To investigate the DNA methyltransferase 1 (DNMT1)expression and the changes in the methylation status of hMLH1 and hMSH2 genes in the tumor tissues and adjacent tissue specimens of non-small-cell lung cancer (NSCLC). Methods The expression of DNMT1 in 52 lung cancer specimens and adjacent tissue specimens was detected by real-time fluorescent quantitative PCR (FQ-PCR). Meanwhile,promoter methylation status of hMLH1 and hM-SH2 was detected by methylation-specific PCR (MSP). Correlation of DNMT1 expression with methylation of hMLH1 and hMSH2 genes was analyzed by Spearman correlation analysis. Results The expression of DNMT1 mRNA in 52 cases of NSCLC specimens and adjacent tissue specimens was 3. 1623 ± 0. 5125 and 2. 8731 ± 0. 3706 (P < 0. 001). The posi-tive rate of promoter methylation of hMLH1 in the lung cancer specimens was higher than that in the adjacent tissue speci-mens [53. 8%(28 / 52)vs. 32. 7% (17 / 52),χ2 = 4. 740,P < 0. 05]. The positive rate of promoter methylation of hM-SH2 in the cancer specimens was higher than that in the adjacent tissue specimens [57. 7%(30 / 52)vs. 34. 6%(18 / 52),χ2 = 5. 571,P < 0. 05]. Methylation status of hMLH1 and hMSH2 was not correlated with the patients'gender,age,tumor size,pathological types,lymph node metastasis,and invasion of surrounding tissues (all P > 0. 05). The expression of DNMT1 was positively correlated with the methylation level of hMLH1 and hMSH2 (r = 0. 479,0. 528,all P < 0. 05). Conclusion DNMT1 is highly expressed in the NSCLC tissues and the DNMT1expression is positively correlated with the promoter methylation levels of hMLH1 and hMSH2 genes,and the expression of these three parameters is not correlated with the clinicopathological features of NSCLC.