食管癌高危人群筛查的MDM2-BRCA2-MGMT自身抗体联合检测试剂盒研究

Development of Molecular Marker Detection Kit with MDM2-BRCA2-MGMT Autoantibodies for Early Detection of Esophageal Cancer

目的建立一种联合检测MDM2、BRCA2和MGMT自身抗体的食管癌高危人群筛查ELISA试剂盒,并探讨其在大规模无症状人群中的推广价值。方法利用间接酶联免疫吸附试验对食管癌组和对照组进行相关血清自身抗体检测,比较其表达差异;在食管癌高发区对无症状人群行血清学检测,且对所有受试者行色素内镜检测,比较检测结果;在食管癌高发区对大规模无症状人群进行筛查,并对血清学检查阳性受试者行色素内镜检查,了解早期癌检出情况。结果3种食管癌相关自身抗体联检食管癌患者阳性率比对照组升高8.52倍(89.50%VS 10.50%),敏感度和特异度均为89.50%;对高发区403例无症状人群3种自身抗体联合检测发现,阳性90例(22.25%);进一步对403人全部行色素内镜和黏膜活检发现,自身抗体阳性组食管癌和癌前病变数量显著多于阴性组;自2011年起对河北磁县地区19415例无症状人群进行食管癌筛查,共发现3980例高易感人群(20.50%);对3980例高危人群进一步行色素内镜和黏膜活检病理检查,共发现1553例癌前病变(39.02%);504例早期食管癌(12.67%)。结论MDM2、BRCA2和MGMT这3种食管癌血清自身抗体联合的ELISA试剂盒,可以更精确筛出无症状的高危人群和早期癌,降低内镜筛查人数、筛查成本,可在食管癌高发区大规模推广应用。

Objective To develop an ELISA kit that can quickly detect the high-risk and early-stage esophageal cancer patients through serum markers related to esophageal cancer(MDM2 protein,BRCA2 protein,and MGMT protein),and to explore the value of using the kit applying among large-scale asymptomatic subjects.Methods Indirect immunoenzyme-linked method was used to detect the relevant autoantibedies(MDM2,BRCA2,MGMT)in the esophageal cancer group and the control group,and compare the expression differences between them.In the high-risk area of esophageal cancer,early selection was performed among the asymptomatic population,then chromoendoscopy was used on positive subjects to find the early cancer detection.Results The positive rate of combined detection of the 3 autoantibedies in esophageal cancer patients was 8.52 times higher than that in the control group(89.50%vs10.50%),and the sensitivity and specificity were 89.50%and 89.50%,respectively.Among 403 asymptomatic people in high incidence area,90 cases(22.25%)were positive by this method.Chromoendoscopy and mucosal biopsy were performed on all 403 people to find that the number of esophageal cancer and precancerous lesions in the autoantibody positive group was significantly higher than that in the negative group.This kit was applied to 19415 asymptomatic subjects in Cixian County to screen high risk of esophageal cancer since2011 and revealed a total of 3980 high-susceptible groups(20.50%)in which chromoendoscopy and mucosal biopsy pathological examinations were used and found 1553 precancerous lesions(39.02%)and 504 early esophageal cancer(12.67%).Conclusion The enzyme-linked immunoassay ELISA kit of combining MDM2,BRCA2 and MGMT,can screen out asymptomatic high-risk subjects and early esophageal cancer more accurately.The kit can significantly reduce the number of endoscopic screening and the cost of investigation.It can be widely applied in high-risk areas of esophageal cancer.