MGMT、h MLH1基因在人脑胶质瘤中的表达及对常见药物化疗敏感性的影响研究

Expression of MGMT and h MLH1 in glioma and its influence on chemosensitivity to common drugs

目的研究O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)、错配修复基因(h MLH1)基因在人脑胶质瘤组织中的表达情况及其对多种常见药物化疗敏感性的影响。方法于2017年6月至2020年10月本院行开颅手术切除的80例胶质瘤石蜡切片标本,按照2∶1比例于同一时期抽取40例患者经脑外伤减压切除的正常脑组织切片标本,均采用免疫组化法检测两种标本中MGMT和h MLH1基因表达情况,并采用组织块培养-终点染色-计算机图像分析法完成(TECIA)药敏检测,以分析其对常见药物化疗敏感性的影响。结果脑胶质瘤、正常脑组织中MGMT基因阳性表达率,hMLH1基因阳性表达率比较差异均有统计学意义(P<0.05)。4种不同病理类型脑胶质瘤组织MGMT与h MLH1基因表达差异无统计学意义(P>0.05),而病理分级Ⅱ级、Ⅲ级、Ⅳ级脑胶质瘤组织中MGMT与h MLH1基因阳性表达率依次升高,差异有统计学意义(P<0.05)。洛莫司汀、替尼泊苷、替莫唑胺敏感率与病理分级有关(P<0.05),且MGMT、TopoⅡ阳性表达洛莫司汀、福莫司汀、替尼泊苷、尼莫司汀、替莫唑胺敏感率均明显低于阴性表达(P<0.05)。结论MGMT和h MLH1基因在人脑胶质瘤标本中阳性表达率较高,且其可影响多种药物化疗敏感性。

Objective To study the expression of O6-methylguanine-DNA methyltransferase(MGMT)and human mismatches repair gene(h MLH1)in glioma tissues and its influence on chemosensitivity to common drugs.Methods The paraffin section specimens of 80 patients with glioma treated by craniotomy and resection in Zhumadian Central Hospital between June 2017 and October 2020 were collected.According to the ratio of 2∶1,the normal brain tissue section specimens of 40 patients undergoing decompression for brain trauma were collected during the same period.Immunohistochemistry was used to detect the expression of MGMT and h MLH1 in the two kinds of specimens,and the tissue culture end point staining computer image analysis(TECIA)was used for drug sensitivity test to analyze the influence on chemosensitivity to common drugs.Results There were statistically significant differences in the positive expression rates of MGMT and h MLH1 in glioma and normal brain tissues(P<0.05).There were no statistically significant differences in the expression of MGMT and h MLH1 in the four different pathological types of glioma tissues(P>0.05).The positive expression rates of MGMT and h MLH1 in pathological gradeⅡ,Ⅲ,andⅣglioma tissues increased successively(P<0.05).Lomustine,teniposide,and temozolomide were related to pathological grade(P<0.05).The sensitivity rates to lomustine,fotemustine,teniposide,nimustine,and temozolomide were all significantly lower in patients with positive expression of MGMT and TopoⅡthan in those with negative expression(P<0.05).Conclusion The positive expression rates of MGMT and hMLH1 in glioma specimens are high,and they can affect chemosensitivity to multiple drugs.