【摘要】 目的探讨液体活检技术在筛查早期食管癌和高危人群中的应用价值。方法利用间接酶联免疫吸附试验对早期食管癌组和对照组进行5种血清肿瘤相关抗原自身抗体[乳腺癌耐药蛋白(BCRP)、人端粒酶逆转录酶(hTERT)、B细胞淋巴瘤/白血病-2相关X蛋白(BAX)、血管内皮生长因子(VEGF)和多药耐药相关蛋白(MRP)]检测,并比较其表达差异。在食管癌高发区对无症状人群进行液体活检技术检测和色素内镜检查,比较2种方法检测结果。采用液体活检技术在食管癌高发区行大规模无症状人群筛查,并对阳性者行色素内镜检查,确认食管癌检出情况。结果 5种肿瘤相关抗原自身抗体组合联合检测的敏感性86.94%,特异性82.45%。对豫北食管癌高发区某镇流行病学调查纳入食管癌筛查的无症状人群1 755例进行液体活检,与色素内镜检查结果比对后发现,阳性者癌前病变和早期食管癌检出分别为62例(26.27%)、32例(13.73%),均高于阴性者的40例(2.63%)、15例(0.99%),差异均有统计学意义(χ~2=208.493,P<0.001;χ~2=123.868,P<0.001)。对湖北钟祥、新疆乌鲁木齐、江苏南京流行病学调查,纳入的无症状人群6 325例进行液体活检,结果发现阳性(高危)人群1 018例,然后进行色素内镜检查,结果发现正常567例(8.96%)、癌前病变286例(4.52%)、食管癌[149例(2.36%),其中早期食管癌130例(2.06%)、晚期食管癌19例(0.30%)]、其他上消化道肿瘤16例(0.25%)。结论 BCRP、hTERT、BAX、VEGF和MRP组合的液体活检技术是早期食管癌和高危人群筛查的有效方法,显著减少了色素内镜检查对象,降低了筛查成本,具有明显的人群推广应用价值。更多还原

【Abstract】 Objective To explore the application value of liquid biopsy in the screening of early esophageal cancer and high risk population. Methods Indirect enzyme-linked immunosorbent assay was used to detect 5 kinds of serum tumor associated antigen autoantibodies [breast cancer resistance protein(BCRP), human telomerase reverse transcriptase(hTERT), B cell lymphoma/leukemia-2 X protein(BAX), vascular endothelial growth factor(VEGF) and multidrug resistance associated protein(MRP)] in the early esophageal cancer group and the control group. Liquid biopsy and pigment endoscopy were performed in the asymptomatic population in areas with high incidence of esophageal cancer, and the results of the two methods were compared. Liquid biopsy technique was used to screen large scale asymptomatic population in areas with high incidence of esophageal cancer, and pigment endoscopy was performed on positive patients to confirm the detection status of esophageal cancer. Results The sensitivity and specificity of 5 kinds of serum tumor associated antigen autoantibody combinations were respectively 86.94% and 82.45%. In the epidemiological investigation in the areas with high incidence of esophageal cancer from Northern Henan Province, 1 755 patients with esophageal cancer received the liquid biopsy and pigment endoscopy. Of the positive liquid biopsy patients, 62 patients(26.27%) with precancerous lesions and 32 patients(13.73%) with early esophageal cancer were found, 40 patients(2.63%) and 15 patients(0.99%) were respectively found in the negative liquid biopsy patients(χ~2 = 208.493, P<0.001; χ~2=123.868, P<0.001). Of the epidemiological investigation in the Zhongxiang, Urumqi and Nanjing, 6 325 patients with asymptomatic population received the liquid biopsy, and 1 018 patients showed the positive(high risk) results. The 1 018 patients received pigment endoscopy, the results showed that normal in the 567 patients(8.96%), precancerous lesions in the 286 patients(4.52%), esophageal cancer in the 149 patients(2.36%) [130 patients(2.06%) with early esophageal cancer, 19 patients(0.30%) with advanced esophageal cancer] and other upper gastrointestinal tumor in the 16 patients(0.25%). Conclusion Liquid biopsy with BCRP, hTERT, BAX, VEGF and MRP is an effective method for screening early esophageal cancer and high risk population, which significantly reduces the objects of pigment endoscopy and the cost of screening, and has obvious population promotion and application value.更多还原