何娅娣?吴振权?侯国良

【摘要】目的 探討血浆环状RNA_0002867（circ_0002867）对HBV相关性肝细胞癌（肝癌）的诊断价值。方法 分析已发表的测序结果，筛选在肝癌患者的组织和血浆中同时高表达的环状RNA，通过微滴数字PCR（ddPCR）检测35例HBV相关性肝癌患者（肝癌组）及30例HBV相关性肝硬化患者（肝硬化组）血浆circ_0002867表达水平，电化学发光法检测2组患者的血清甲胎蛋白水平，应用受试者工作特征（ROC）曲线分析血浆circ_0002867、血清甲胎蛋白及两者联合对HBV相关性肝癌的诊断价值。结果 在肝癌患者的组织和血浆中同时高表达的环状RNA中取交集筛选出circ_0002867行进一步验证。肝癌组血浆circ_0002867表达水平为（29.63±11.56）copies/ml，高于肝硬化组的（19.15±11.57）copies/ml（P < 0.001）;血浆circ_0002867、血清甲胎蛋白及两者联合诊断HBV相关性肝癌的ROC曲线下面积分别为0.725（95% CI 0.600～0.828）、0.670 （95% CI 0.542～0.781）、0.810（95%CI 0.693～0.896），血浆circ_0002867和血清甲胎蛋白两者联合提高了血清甲胎蛋白诊断HBV相关性肝癌的效能（P < 0.05）。结论 血浆circ_0002867联合血清甲胎蛋白对诊断HBV相关性肝癌具有较好的临床价值。

【关键词】乙型肝炎病毒;肝细胞癌;诊断;血浆;甲胎蛋白;环状核糖核酸

Plasma circular RNA_0002867 as a diagnostic biomarker for hepatitis B virus-related hepatocellular carcinoma He Yadi， Wu Zhenquan， Hou Guoliang. Health Management Center， the Third Affiliated Hospital of Sun Yat-sen University， Guangzhou 510630， China

Corresponding author， He Yadi， E-mail： heyadi2015@ 126. com

【Abstract】Objective To investigate the diagnostic value of plasma circular RNA_0002867 （circ_0002867） for hepatitis B virus （HBV）-related hepatocellular carcinoma （HCC）. Methods The published sequencing results were analyzed to screen the high expression of circular RNAs in both tissues and plasma of HCC patients. The expression levels of plasma circ_0002867 were detected by digital droplet polymerase chain reaction （ddPCR） in 35 patients with HBV-related HCC and 30 patients with HBV-related liver cirrhosis. The serum alpha-fetoprotein （AFP） levels were determined by electrochemiluminescence in two groups. The receiver operating characteristic （ROC） curve was delineated to analyze diagnostic values of plasma circ_0002867， serum AFP and these two combined for HCC. Results The circ_0002867， which was highly expressed in both tissues and plasma of HCC patients， was screened for subsequent validation. The expression level of plasma circ_0002867 in the HBV-related liver cirrhosis group was significantly lower than that in the HBV-related HCC group （（19.15±11.57） copies/ml vs. （29.63±11.56） copies/ml; P < 0.001））. The area under ROC for plasma circ_0002867， serum AFP， and these two combined was 0.725 （95% CI 0.600-0.828）， 0.670 （95% CI 0.542-0.781） and 0.810 （95% CI 0.693-0.896）， respectively. The combination of serum AFP and plasma circ_0002867 significantly improved the diagnostic accuracy of serum AFP for HBV-related HCC （P < 0.05）. Conclusion Plasma circ_0002867 combined with serum AFP is a potential diagnostic biomarker for HBV-related HCC in clinical practice.

【Key words】Hepatitis B virus;Hepatocellular carcinoma; Diagnosis;Plasma;Alpha-fetoprotein;

Circular RNA

肝细胞癌（肝癌）主要由HBV感染引起，是我国第2常见的消化系统实体瘤，也是恶性肿瘤死亡的第2大原因[1]。肝癌的高病死率与其早期缺乏临床癥状、在发现时大部分已处于晚期密切相关[2]。目前临床上常用的血清甲胎蛋白诊断肝癌的灵敏度和特异度分别为39% ～ 64%和76% ～ 91%，其效能仍有待提高[3]。一项多中心的回顾性研究表明，Cmi（7个血清微RNA的组合）诊断肝癌的灵敏度和特异度分别为70% ～ 86%和80% ～ 91%[4]。环状RNA （circRNA）与微RNA同属于非编码RNA。与微RNA相比，circRNA具有闭合环状结构，可耐受核酸外切酶，稳定性更高。有研究显示，血浆组合circRNA （circ_0000976，circ_0007750和circ_0139897）对直径≤3 cm的肝癌具有较高的诊断效能，优于血清甲胎蛋白[5]。本研究分析已发表circRNA测序结果，采用微滴数字PCR （ddPCR）检测技术，探索血浆circRNA对诊断HBV相关性肝癌的价值，现报告如下。……