Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China.
Biosci Rep. 2020 Mar 27;40(3). doi: 10.1042/BSR20194127.
O6-methylguanine-DNA methyltransferase (MGMT) is a specific DNA damage reversal repair protein. The influence of MGMT status on alkylating agent sensitivity in patients with neuroendocrine neoplasms (NENs) is controversial. We conducted a meta-analysis to assess the influence of MGMT status on the therapeutic sensitivity of alkylating agents in patients with NENs.
We searched PubMed, EmBase, and Cochrane library public databases through 3 July 2019. The objective response rate (ORR) was the outcome data of interest. Subgroup analysis was performed according based on MGMT methylation and expression of MGMT protein.
Eleven studies were included in the meta-analysis. The proportion of patients with NENs that achieved an ORR after alkylating agent treatment was higher in the MGMT-deficient group than the non-deficient group (OR: 5.00; 95% CI: 3.04-8.22; P < 0.001; I2: 3%). Similar results were noted in the MGMT methylation and MGMT protein expression subgroups.
Patients with NENs and MGMT methylation or low protein expression had a higher ORR proportion than patients without MGMT methylation or high protein expression. The MGMT status can be used as a biological indicator of the response to alkylating agent treatment in patients with NENs.
O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）是一种特定的 DNA 损伤逆转修复蛋白。MGMT 状态对神经内分泌肿瘤（NENs）患者烷化剂敏感性的影响存在争议。我们进行了一项荟萃分析，以评估 MGMT 状态对 NENs 患者烷化剂治疗敏感性的影响。
我们通过 2019 年 7 月 3 日检索了 PubMed、Embase 和 Cochrane 图书馆公共数据库。客观缓解率（ORR）是感兴趣的结果数据。根据 MGMT 甲基化和 MGMT 蛋白表达情况进行亚组分析。
荟萃分析纳入了 11 项研究。在接受烷化剂治疗后，MGMT 缺陷组 NENs 患者的 ORR 比例高于非缺陷组（OR：5.00；95%CI：3.04-8.22；P<0.001；I2：3%）。在 MGMT 甲基化和 MGMT 蛋白表达亚组中也观察到了类似的结果。
MGMT 甲基化或低蛋白表达的 NENs 患者比无 MGMT 甲基化或高蛋白表达的患者具有更高的 ORR 比例。MGMT 状态可作为 NENs 患者对烷化剂治疗反应的生物标志物。
