MGMT、ERCC2基因对替莫唑胺治疗恶性胶质瘤耐药性的影响及其表达相关性

Comparison of MGMT and ERCC2 expression in temozolomide for the treatment of malignant glioma drug resistance and their genetic relationship

目的 研究人脑胶质瘤组织中两种耐药基因MGMT、ERCC2对于替莫唑胺治疗恶性胶质瘤产生耐药性的影响及两种耐药基因表达上的相关关系.方法 将58例应用替莫唑胺化疗的恶性胶质瘤患者经随诊分为治疗敏感组和不敏感组,58例患者年龄为19～68岁,其中治疗敏感组28例,治疗不敏感组30例.利用免疫组化的方法分析MGMT、ERCC2的表达率,用免疫组化以及RT-PCR的方法分析两种基因表达相关性.结果 在替莫唑胺治疗敏感组中MGMT、ERCC2阳性表达率分别为10.71%、3.57%,不敏感组中MGMT、ERCC2阳性表达率分别为63.33%、56.67%;并且MGMT、ERCC2的表达经免疫组化和RT-PCR方法分析均具有明显相关性（均P＜0.01）.结论 MGMT、ERCC2基因表达在替莫唑胺治疗敏感患者的表达率明显低于治疗不敏感患者表达率,两种基因的表达对肿瘤的预后可能相关,且两种基因表达之间具有一定的相关性,可能共同参与细胞DNA损伤的修复,形成肿瘤耐药.

Objective To study the impact of two human glioma tissue resistance genes MGMT and ERCC2 on the temozolomide-based treatment of malignant gliomas and detect the relationship of their expressions. Methods A total of 58 malignant glioma patients aged 19 -68 years old receiving a chemotherapy of temozolomide were followed up and classified as non-sensitive group （n = 30） and sensitive group （n = 28）. Immunohistochemistry was employed to detect the expression rates of MGMT and ERCC2.And the correlation between the expressions of two genes was analyzed by immunohistochemistry and RT-PCR （reverse transcription-polymerase chain reaction）. Results The expression rates of MGMT and ERCC2were 10. 71% and 3.57% in the sensitive group and 63.33% and 56. 67% in the non-sensitive group. It had an obvious correlation with the expressions of MEGT and ERCC2 through an analysis of immunohistochemistry and RT-PCR （both P 〈0. 01 ）. Conclusion The expressions of MGMT and ERCC2in the sensitive group are markedly lower than those in the non-sensitive group. The expression of two genes may be related to tumor prognosis. Maybe these two genes have an intrinsic link between their expressions.Both participate in the repair of cellular DNA damage and the formation of tumor drug resistance. And the prognosis has obvious relevance.