CpG岛甲基化表型肺癌的分型标记及临床病理特征

Biomarkers and clinicopathologic features of CpG island methylator phenotype lung cancer

目的比较新的Cp G岛甲基化表型(CIMP)筛选标记基因和经典CIMP筛选标记基因在CIMP肺癌筛选中的作用,并分析CIMP肺癌的临床病理特征。方法取第二军医大学长海医院呼吸科50例肺癌患者的肺癌组织和癌旁组织,提取DNA,进行甲基化转换后,利用甲基化特异性PCR(MSP)对新的CIMP筛选标记基因(SHISA3、CTSL1、C1ORF103和TMEM200B)和经典的CIMP筛选标记基因(CACNA1G、IGF2、NEUROG1、RUNX3)的启动子Cp G岛区域进行扩增,采用琼脂糖凝胶电泳分析其甲基化状态。运用SPSS统计软件对结果进行统计分析。结果肺癌组织发生明显的甲基化,所研究的8个基因甲基化水平均明显高于癌旁组织(P=0.014)。其中RUNX3甲基化与淋巴结转移及功能状态(PS)评分有关(P值分别为0.017、0.018)。年龄>60岁的肺癌患者甲基化率高于≤60岁者(P=0.031)。吸烟对CTSL1基因甲基化的影响也很大(P=0.018)。结论 Cp G岛甲基化表型肺癌具有独特的临床病理特征;新的和经典的甲基化基因组合在CIMP肺癌筛选上都具有较高的灵敏度和特异性。

Objective To compare the sensitivity and specificity of the new CpG island methylation phenotype （CIMP） selection marker with the classical CIMP selection marker, and to analyze the clinical pathological features of CIMP lung cancer. Methods Genomic DNA was extracted from 50 cases of lung cancer tissues and the corresponding adjacent normal lung tissues in Changhai Hospital. Methylation statues of new CIMP selction marker （SHISA3, CTSL1, C10RFI03 and TMEM2OOB） and the classical CIMP selection markers （CACNAIG, IGF2, NEUROG1 and RUNX3） were determined by methylation specific PCR, and the results were analyzed by SPSS software. Results Notable methylation was found in the lung caner tissues, with the methylation levels of the eight studied genes in the lung cancer tissues being significantly higher than those in the adjacent tissues （P=0. 014）. RUNX3 gene methylation was significantly related to lymph node metastasis and PS score （P=0. 017, P=0. 018）. The methylation rate in lung cancer patients aged over 60 was significantly higher than those aged younger than 60 years old （P：0. 031）. Smoking showed significant influence on CTSL1 gene methylation （P=0. 018）. Conclusion CpG island methylation phenotypic lung cancer has unique clinical pathological features. Both the new and classic CIMP markers are of high sensitivity and specificity for the diagnosis of lung cancer.