摘要
目的多重耐药(drug resistance,MDR)是肿瘤化疗失败的主要原因。本研究旨在探讨MDR1甲基化对宫颈癌经皮子宫动脉血管腔内化疗栓塞疗效的影响。方法选择67例宫颈癌患者接受栓塞化疗,45例正常宫颈组织作为对照。免疫组化检测宫颈癌中P-糖蛋白(P-gp)水平,并与正常组织进行比较。通过使用特异性千碱基裂解法和基质辅助激光解吸电离飞行时间质谱法分析MDR1基因启动子区16个CpG岛的甲基化状态。结果P-gp在正常宫颈组织中的阳性表达率为0%(0/45),介入栓塞化疗前后的阳性表达率分别为61.19%(41/67)和77.61%(52/67)。宫颈癌组织与正常宫颈组织相比有明显差异(χ2=4.2523,0.0392)。化疗前P-gp的阳性表达率与化疗疗效呈负相关(r=-0.340,P=0.005)。正常组织中13个CpG岛的甲基化率显著高于宫颈组织(P<0.05)。在宫颈癌组织中,经皮子宫动脉血管腔内化疗栓塞前6个CpG岛的甲基化率高于化疗后,但1个CpG岛的甲基化率低于化疗后(P<0.05)。化疗前有效化疗的1个CpG岛甲基化率明显高于无效化疗(P<0.05),其他CpG岛相似(P<0.05)。结论MDR1编码的P-gp表达水平,部分MDR1基因启动子区CpG岛的甲基化状态,与宫颈癌介入栓塞化疗的疗效密切相关。
Objective Multidrug resistance(MDR)is the main cause of tumor chemotherapy failure.This study aims to explore the influence of MDR1 methylation on curative effect of transcatheter arterial chemoembolization for cervical cancer.Methods 67 patients with cervical cancer underwent transcatheter arterial chemoembolization were selected,and 45 cases of normal cervical tissues were included as a control group.Immunohistochemistry was used to detect the level of P-glycoprotein(P-gp)in cervical cancer,and compared with normal tissues.The methylation status of the MDR1 gene promoter region 16 CpG units was analyzed by using kilobase-specific cracking and matrix-assisted laser desorption ionization time of flight mass spectrometry.Results The results indicated that the positive expression rates of P-gp were 0%(0/45)in normal cervical tissue,and 61.19%(41/67)and 77.61%(52/67)before and after transcatheter arterial chemoembolization in cervical cancer tissues,respectively.There were significant differences between cervical cancer tissues and normal cervical tissues(χ2=4.2523,0.0392).The positive expression rate of P-gp before chemotherapy was negatively correlated with efficacy of chemotherapy(r=-0.340,P=0.005).Methylation rate of 13 CpG units in normal tissues was significantly greater than that in cervical tissues(P<0.05).In cervical cancer tissue,methylation rate of six CpG units before transcatheter arterial chemoembolization was higher than that after chemotherapy,but one CpG unit was lower than that after chemotherapy(P<0.05).The methylation rate of one CpG unit with effective chemotherapy before chemotherapy was significantly higher than ineffective chemotherapy(P<0.05),and the other CpG units were similar(P<0.05).Conclusions P-gp expression level coded by MDR1,methylation status of partial MDR1 gene promoter regions CpG island,is closely related to the efficacy of transcatheter arterial chemoembolization for cervical cancer.
作者
张悦
顾福嘉
Zhang Yue;Gu Fujia(Department of Interventional,Guizhou Provincial Hospital,Guizhou Guiyang 550002,China)
出处
《中华介入放射学电子杂志》
2020年第1期51-56,共6页
Chinese Journal of Interventional Radiology：electronic edition
作者简介
通信作者:顾福嘉,Email:gfjyy@163.com。
