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目的 探讨DNA错配修复 (MMR)基因mRNA在肺癌组织中的表达及其与微卫星改变关系。方法 用RT PCR和PCR -变性聚丙烯酰胺凝胶电泳 -银染法 ,检测 46例原发性肺癌组织中 5种MMR基因mRNA表达及 6种微卫星改变。结果 5种MMR基因mRNA在肺癌组织中表达降低的发生率为 13 .0 %～ 3 2 .6% ,至少一种基因mRNA表达降低的发生率为 5 8.7% ( 2 7/46)。 3 9.1% ( 18/46)病例有至少 2种基因mRNA下调。淋巴结转移阳性者的MMR基因mRNA表达降低发生率 ( 2 0 /2 7,74.1% )较淋巴结转移阴性者 ( 7/19,3 6.8% )显著增高 (P <0 .0 2 5 )。mRNA表达下调在微卫星不稳定性 (MSI)和 /或杂合性丢失 (LOH) (≥ 2个位点 )阳性患者中占 95 .8% ( 2 3 /2 4) ,而在阴性患者中占 18.2 % ( 4 /2 2 ) ,两者差异显著 (P <0 .0 0 5 )。结论 肺癌组织中错配修复功能降低 ,且与微卫星改变有关 ,它在肺癌发病中可能有一定作用
Objective To investigate the expression of DNA mismatch repair (MMR) mRNA in lung cancer tissues and its relationship with microsatellite changes. Methods RT-PCR and PCR-denaturing polyacrylamide gel electrophoresis-silver staining were used to detect the mRNA expression of 5 kinds of MMR gene and 6 kinds of microsatellite changes in 46 cases of primary lung cancer. RESULTS: The decrease in the expression of 5 MMR gene mRNAs in lung cancer tissues was 13.0 % to 32.6%, and the incidence of at least one gene mRNA expression was 58.7 % ( 2 7/46). 3 9.1% (18/46) cases had at least 2 genes downregulated. The incidence of decreased expression of MMR gene mRNA was significantly higher in lymph node metastasis patients (2 0 /27 7,74.1%) than in those with negative lymph node metastasis (7/19, 3 6.8%) (P < 0.05). Down-regulation of mRNA expression accounted for 95.8% (23/24) of patients with positive microsatellite instability (MSI) and/or loss of heterozygosity (LOH) (≥ 2 sites), but in negative patients Accounting for 18.2% (4/22), the difference was significant (P < 0.05). Conclusions Mismatch repair function in lung cancer tissues is reduced and related to microsatellite changes. It may play a role in the pathogenesis of lung cancer.