Correlation between promoter hypermethylation of GSTP1 and response to chemotherapy in diffuse large B cell lymphoma
Correlation between promoter hypermethylation of GSTP1 and response to chemotherapy in diffuse large B cell lymphoma
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DOI：
10.1007/s00277-007-0299-1
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发表时间：
2007-08-01
影响因子：
3.5
通讯作者：
Aozasa, Katsuyuki
中科院分区：
文献类型：
--
作者：
Nakamichi, Itsuko;Tomita, Yasuhiko;Aozasa, Katsuyuki
谷胱甘肽-S-转移酶P1和O-6-甲基鸟嘌呤脱氧核糖核酸甲基转移酶与阿霉素等化疗药物耐药有关。本研究分析弥漫性大B细胞淋巴瘤(DLBCL)中GSTP1、MGMT基因启动子高甲基化、MGMT及死亡相关蛋白激酶(DAPK)基因启动子甲基化对预后的影响。分析了53例DLBCL患者，其中男性24例，女性29例，年龄从23岁到91岁(中位数65岁)。采用甲基化特异性聚合酶链式反应和定量逆转录聚合酶链式反应(RT-PCR)分析冻存DLBCL的基因组DNA和总RNA，检测GSTP1、MGMT和DAPK基因启动子的高甲基化状态和基因表达。免疫组织化学方法检测GSTP1和MGMT在蛋白水平的表达。53例患者中GSTP1、MGMT和DAPK基因启动子甲基化分别为12例(22.6%)、21例(39.6%)和36例(67.9%)。定量RT-PCR和免疫组织化学均未显示甲基化状态与GSTP1和MGMT的mRNA和蛋白表达之间的相关性。GSTP1启动子高甲基化患者的5年总生存率高于无GSTP1启动子甲基化患者(100vs62.2%；p<；0.05)。然而，在多因素分析中，GSTP1启动子高甲基化并不是一个独立的预后因素。GSTP1基因甲基化状态可作为DLBCL的药物反应指标和预后指标。
Glutathione-S-transferase P1 (GSTP1) and O-6-methylguanine DNA methyltransferase (MGMT) are involved in drug-resistant to chemotherapeutic agents such as doxorubicin. In this study, prognostic significance of promoter hypermethylation and mRNA and protein expression of GSTP1 and MGMT together with promoter hypermethylation of death-associated protein kinase (DAPK) in diffuse large B cell lymphoma (DLBCL) was analyzed. Fifty-three patients with DLBCL, 24 men and 29 women, with age ranging from 23 to 91 (median 65), were analyzed. Genomic DNA and total RNA extracted from frozen samples of DLBCL were analyzed by methylation-specific polymerase chain reaction and quantitative reverse transcription polymerase chain reaction (RT-PCR) to determine promoter hypermethylation and mRNA expression of GSTP1, MGMT, and DAPK. Immunohistochemical analysis was performed to determine GSTP1 and MGMT expression at the protein level. Promoter hypermethylation of GSTP1, MGMT, and DAPK was detected in 12 (22.6%), 21 (39.6%), and 36 (67.9%) of 53 patients, respectively. Quantitative RT-PCR and immunohistochemistry did not show a correlation between methylation status and mRNA and protein expression of GSTP1 and MGMT. Patients with GSTP1 promoter hypermethylation showed a better 5-year overall survival rate than those without (100 vs 62.2%; p < 0.05). However, GSTP1 promoter hypermethylation was not an independent prognosticator in multivariate analysis. Methylation status of GSTP1 could be an indicator of drug response and a prognosticator for DLBCL.