胃癌患者血清抑癌基因启动子超甲基化测定的临床意义

摘要

目的：探讨胃癌患者血清中抑癌基因超甲基化检测的临床意义。方法随机收集2011～2013年上海市静安区中心医院进行胃镜检查的患者，32例胃癌患者为胃癌组，29例萎缩性胃炎为萎缩性胃炎组和30例健康者为健康对照组。应用甲基化特异性PCR（MSP）方法，测定血清Ras相关区域家族基因1a（RASSFA1）基因、人类相关转录因子3（Runx3）基因、错配修复蛋白MutL同源物1（hmLH1）基因、多肿瘤抑制基因1（MTS1）也称P16基因、上皮E钙粘蛋白（E-Cadherin）基因、组织因子途径抑制物2（TFPI-2）基因启动子甲基化状态。结果胃癌组血清RASSF1A、RUNX3、hmLH1、P16、E-Cadherin、TFPI-2基因超甲基化阳性率分别为21．9％，40．6％，21．9％，34．4％，28．1％，28．1％；萎缩性胃炎组分别为3．5％，13．8％，0．0％，6．9％，3．5％，6．9％；对照组仅检出RUNX3基因启动子甲基化，阳性率3．5％；胃癌组血清6种基因启动子甲基化阳性率均明显高于萎缩性胃炎组和健康对照组（P＜0．05）。联合血清中6种基因启动子甲基化对胃癌诊断灵敏度为76．7％，较单独一个基因明显升高（P＜0．05）；特异性为86．5％，与RUNX3基因比较，差异无统计学意义（P＞0．05），与其他5个基因单独测定特异性降低（P＜0．05）。结论 MSP检测能检测到血清中RASSF1A、RUNX3、hmLH1、P16、E-Cadherin、TFPI-2基因启动子超甲基化。6个基因启动子联合测定对胃癌诊断的灵敏度更高，可为胃癌的诊断、治疗以及判断预后提供新方法或依据。%Objective To explore the clinical significance of tumor suppressor genes promoter hypermethyla-tion determination in sera of patients with gastric cancer .Methods Thirty two patients suffered from gastric cancer ( gastric cancer group) and 29 patients with atrophic gastritis (atrophic gastritis group)were randomly recruited in this study ,thirty healthy people were recruited as control group .The serum of patients were detected by MSP method for RASSF1A ,RUNX3 ,hmLH1 ,P16 ,E-Cadherin and TFPI-2 gene promoter hypermethylation .Results The positive rates of RASSF1A ,RUNX3 ,hmLH1 ,P16 ,E-Cadherin and TFPI-2 gene promoter hypermethylation in sera were 21 .9% ,40 .6% ,21 .9% ,34 .4% ,28 .1% and 28 .1% respectively in gastric cancer group ,as well as 3 .5% ,13 .8% , 0 .0% ,6 .9% ,3 .5% and 6 .9% in atrophic gastritis group .Only RUNX3 gene promoter hypermethylation in serum were detected in the control group ,the positive rate was 3 .45% .The positive rates of six kinds of gene promoter hy-permethylation in gastric cancer were respectively higher than the control group (P< 0 .05 ) and atrophic gastritis group (P<0 .05 ) .The sensitivity of combined detection of six gene promoter hypermethylation as 76 .7% was supe-rior to a single gene for diagnosis of gastric cancer (P<0 .05 ) .But the specificity of the combined detection was de-creased to 86 .44% compared with five other genes except for RUNX3 respectively (P<0 .05 ) .There was no signifi-cant difference between the combined detection with RUNX3 gene (P>0 .05 ) .Conclusion RASSF1A ,RUNX3 ,hm-LH1 ,P16 ,E-Cadherinand TFPI-2 gene promoter hypermethylation in sera can be detected by MSP .The diagnosis sensitivity for gastric cancer of the six gene promoter hypermethylation combined detection was higher than the single detection of these six gene promoter hypermethylation .The research results provided a novel testing method for clinic diagnosis ,treatment and prognosis judgment for gastric cancer .