MGMT不同表达水平与替莫唑胺对胃肠胰神经内分泌肿瘤疗效的相关性

目的:通过检测肿瘤组织中O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）的表达，探讨其与胃肠胰神经内分泌瘤以替莫唑胺为基础化疗患者预后的相关性。方法:收集2017年至2019年在我院接受替莫唑胺联合替吉奥化疗的15例晚期胃肠胰神经内分泌瘤患者的肿瘤组织，采用免疫组织化学法检测肿瘤组织中MGMT蛋白表达情况，根据表达情况分为MGMT阴性组和MGMT阳性组，并对患者长期随访，进行无进展生存时间和药物安全性的评定，对MGMT表达水平与替莫唑胺治疗效果行相关性分析。结果:15例患者肿瘤组织MGMT表达阴性者为8例（53.3%），MGMT表达阳性者为7例（46.7%）；MGMT阴性组患者化疗6个疗程后，客观缓解率（ORR）为35.7%(3/8)，明显高于MGMT阳性组的0(0/7)；MGMT表达阳性组患者的中位无进展生存时间（mPFS）为6个月，而MGMT表达阴性组患者的mPFS目前无法得出，但明显长于MGMT阳性组，两组间差异具有统计学意义（P=0.000 2）。化疗不良反应均为2级以下的骨髓抑制和消化道反应。结论:基于替莫唑胺化疗方案的疗效与MGMT在肿瘤组织中的表达状态相关，MGMT表达与否可以用作胃肠胰神经内分泌瘤患者对替莫唑胺治疗反应的生物学指标。

Effect of different expression status of MGMT on the efficacy of temozolomide in gastroenteropancreatic neuroendocrine tumors

Objective:To study the expression of O6-methylguanine DNA methyltransferase (MGMT) in tumor tissues and to explore its effect on the prognosis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with temozolomide (TMZ) based chemotherapy.Methods:The tumor tissues of 15 patients with advanced GEP-NETs who received TMZ combined with Tiggio in our hospital from 2017 to 2019 were collected.Immunohistochemistry was used to detect the expression of MGMT protein in the tumor tissues.They were classified as MGMT negative group and MGMT positive group according to the expression.The progression free survival time (PFS) and drug safety were evaluated and analyzed during the follow up period.The correlation analysis between the expression level of MGMT and the treatment effect of TMZ based chemotherapy was performed.Results:Eight cases (53.3%) were negative for MGMT expression in the tumor tissues of 15 patients,and 7 cases (46.7%) were positive for MGMT expression.After 6 courses of chemotherapy,the objective response rate （ORR）of the MGMT negative group was 3/8,which was significantly higher than the 0/7 of the MGMT positive group.The median progression-free survival time (mPFS) of patients in the MGMT expression-positive group was 6 months,while the mPFS of the patients in the MGMT expression-negative group could not be obtained at present,but it was significantly longer than the MGMT-positive group.The difference between the two groups was statistically significant (P=0.000 2).Adverse reactions of chemotherapy were bone marrow suppression and digestive system reactions below grade 2.Conclusion:The efficacy of TMZ chemotherapy is closely related to the expression of MGMT in tumor tissues.The expression of MGMT can be used as a biological indicator of the response of patients with gastrointestinal pancreatic neuroendocrine tumors to TMZ treatment.