联合检测微卫星不稳定性和p16甲基化在早期肺癌中的诊断价值

Diagnostic value of combination detection of p16 methylation and microsatellite instability in early lung cancer

目的研究联合检测微卫星不稳定性(MSI)和p16基因启动子甲基化在早期肺癌中的诊断价值。方法采用PCR单链长度分析法检测肺癌组、肺癌前病变组和正常肺组织组的MSI;采用甲基化特异PCR法检测肺癌组、肺癌前病变组和正常肺组织组p16甲基化。结果癌前病变组MSI的发生率显著高于肺癌组(P<0.05)和正常肺组织组(P<0.01),肺癌组MSI的发生率显著高于正常肺组织组(P<0.01);肺癌组p16甲基化的发生率显著高于癌前病变组(P<0.01)和正常肺组织组(P<0.01),癌前病变组p16甲基化的发生率显著高于正常肺组织组(P<0.01);联合检测MSI和p16甲基化的敏感性显著高于单一检测MSI(P<0.01)和p16甲基化(P<0.05);联合检测法与单一检测MSI和单一检测p16甲基化的特异性比较,无显著性差异(P>0.05)。结论3p上MSI检测和p16甲基化可以作为早期肺癌的诊断指标;联合检测MSI和p16甲基化可以显著提高早期肺癌诊断的敏感性同时不降低其特异性,值得临床推广。

Objective To investigate the diagnostic value of combined detection of p16 methylation and microsatellite instability （MSI） on 3p in early lung cancer. Methods In lung cancer group, precancerous lesion group, and normal lung tissue group, the MSI on 3p was detected at four microsatellite loci by using PCR-single strand length polymorphism-EB staining method and the p16 methylation was detected by using methylation-specific PCR. Results The ratio of MSI was significantly higher in precancerous lesion group than in lung cancer group （ P 〈 0.05 ） and normal lung tissue group（ P 〈 0.01 ）. The ratio of MSI was significantly higher in lung cancer group than in normal lung tissue group （ P 〈 0.01 ）. The ratio of p16 methylation was significantly higher in lung cancer group than in precancerous lesion group （P 〈 0.01 ） and normal lung tissue group （P 〈 0.01 ）. The ratio of p16 methylation was significantly higher in precancerous lesion group than in normal lung tissue group （P 〈 0.01 ）. In the diagnosis of early lung cancer, the sensitivity of combined detection of MSI and p16 methylation was significantly higher than that of single detection （P 〈 0.05 ）, but there was no difference in the specificity between combined detection and single detection of p16 methylation（P 〉0.05）. Conclusion The MSI and p16 gene methylation are helpful markers in the diagnosis of early lung cancer. Combined detection of MSI and p16 gene methylation could significantly increase the sensitivity in the diagnosis of early lung cancer.