MGMT and response to alkylation agents in neuroendocrine tumor:A meta-analysis
MGMT and response to alkylation agents in neuroendocrine tumor:A meta-analysis
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神经内分泌肿瘤中的 MGMT 和对烷化剂的反应：荟萃分析
DOI：
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Xianjun Yu
中科院分区：
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作者：
Heli Gao;Liang Liu;Huaxiang Xu;Wenquan Wang;Chuntao Wu;Shirong Zhang;Jinzhi Xu;Quanxing Ni;Xianjun Yu
烷化剂化疗是治疗神经内分泌肿瘤(NETs)的关键。O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子甲基化对接受烷化剂化疗的NET患者的预测意义仍存在争议。这项荟萃分析描述了MGMT表达和启动子甲基化是否有助于预测烷化剂化疗的净反应。我们在PubMed、EMBASE和Cochrane图书馆中进行了系统的搜索，并确定了描述MGMT状态与患者对烷化剂化疗的净反应之间关系的文章。我们的分析包括10篇文章。免疫组织化学(IHC)法检测的MGMT缺陷率与焦磷酸测序(PSQ)法检测的MGMT启动子甲基化率相似。胰腺网(PNET)患者MGMT缺乏率高于GI-Net患者(p<；0.05)。无论检测方法是IHC(HR 0.39，95%CI 0.17~0.89)还是PSQ(HR 0.33，95%CI 0.19~0.56)，Net和MGMT基因缺失/启动子甲基化患者接受烷化剂化疗后无进展生存期(PFS)显著延长。此外，Net和MGMT缺乏的患者对烷化剂化疗的客观缓解率(ORR)也较好(IHC p=0.01，PSQ p=0.02)。PNET亚组分析显示，MGMT状态和ORR之间没有显著关联。我们的研究结果表明，无论MGMT检测方法如何，MGMT缺乏/启动子甲基化预示着Net患者对烷化药物的良好反应。然而，MGMT缺乏对pNET患者的预测作用有待进一步评估。
Alkylating agent chemotherapy is essential for the treatment of neuroendocrine tumors (NETs)in patients. The predictive significance of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for patients with NET and treated with alkylating agent chemotherapy remains controversial. This meta-analysis describes whether MGMT expression and promoter methylation could help predict NET response to alkylating agent chemotherapy. We conducted a systematic search in PubMed, EMBASE, and the Cochrane library and identified articles describing a relationship between MGMT status and NET response to alkylating agent chemotherapy in patients. Ten articles were included in our analysis. The MGMT deficiency rate measured by immunohistochemistry (IHC) was similar to the MGMT promoter methylation rate measured by pyrosequencing (PSQ). The MGMT deficiency rate was higher in patients with pancreatic NET (pNET) than in patients with GI-NET (p<0.05). Patients with NET and MGMT deficiency/promoter methylation had a significantly longer progression-free survival (PFS) when treated with alkylating agent chemotherapy, regardless of detection method: IHC (HR 0.39, 95% CI 0.17–0.89) or PSQ (HR 0.33, 95% CI 0.19–0.56). Also, patients with NET and MGMT deficiency had a better objective response rate (ORR) to alkylating agent chemotherapy (by IHC p=0.01, by PSQ p=0.02). The pNET subgroup analysis showed no significant association between MGMT status and ORR. Our findings suggest that MGMT deficiency/promoter methylation predicts a favorable response to alkylating agents in patients with NET, regardless of the MGMT detection method. However, the predictive roles of MGMT deficiency in patients with pNET need further assessment.