血浆游离双链DNA在原发性肝癌中的诊断价值

The diagnostic value of cell-free dsDNA in plasma for primary hepatic carcinomas

目的:探讨血浆中游离双链DNA(cell-free double-stranded DNA,cf-dsDNA)在原发性肝癌(primary hepa-tic carcinomas,PHC)诊断中的应用。方法:招募62例PHC患者和41例良性肝病患者以及45例健康对照,填写信息登记表。抽取治疗前患者和健康对照的空腹血样,磁珠法提取血浆cf-dsDNA,Qubit 3.0荧光计测定cf-dsDNA浓度。电化学发光法测定血清中甲胎蛋白(AFP)、糖类抗原19-9(CA19-9)、糖类抗原12-5(CA12-5)和癌胚抗原的水平。分析各组患者血浆cf-dsDNA水平的差异及血浆cf-dsDNA水平与PHC患者临床特征的关系,应用受试者工作特征(ROC)曲线分析cf-dsDNA对PHC的诊断效率。结果:PHC患者术前cf-dsDNA水平的中位数显著高于良性肝病患者和健康对照(H=93.54,P<0.01)。PHC患者中,cf-dsDNA水平在年龄、性别、AFP水平、PHC类型以及肿瘤大小之间均无明显差异(P均>0.05)。cf-dsDNA水平与PHC的TNM分期之间存在等级相关(r_(s)=0.311,P=0.0139)。与传统肿瘤标志物相比,cf-dsDNA诊断PHC效率明显提高(AUC=0.965)。根据cf-dsDNA的临界值(>1.912 ng/μL),cf-dsDNA在PHC中的阳性率为90.32%(56/62),明显高于传统肿瘤标志物(χ^(2)=36.00,P<0.01)。结论:血浆cf-dsDNA是诊断PHC理想的非侵入性指标。

Objective:To explore the clinical application of plasma cell-free double-stranded DNA(cf-dsDNA)in the diagnosis of primary hepatic carcinomas(PHC).Methods:Sixty-two PHC patients and 41 patients with benign liver disease and 45 healthy controls were recruited.All subjects were required to fill in a questionnaire,and the fasting blood samples were taken from healthy individuals and pre-treatment patients.The plasma cf-dsDNA was extracted by magnetic bead method and the concentration was determined by Qubit 3.0 fluorometer.The serum tumor markers AFP,CA19-9,CA12-5 and CEA levels were measured by electrochemiluminescence.The differences in plasma cf-dsDNA levels in each group of patients and the relationship between plasma cf-dsDNA levels and the clinical characteristics of PHC patients were analyzed,and receiver operating characteristic(ROC)curves were used to ana-lyze the diagnostic efficiency of cf-dsDNA for PHC.Results:The median of preoperative cf-dsDNA levels in PHC patients was significantly higher than those in patients with benign liver disease or healthy controls(H=93.54,P<0.01).In PHC patients,there was no difference in cf-dsDNA levels between age,gender,AFP level,PHC type,and tumor_(s)ize(all of P>0.05).There was a certain rank correlation between cf-dsDNA levels and TNM stage of PHC patients(r_(s)=0.311,P=0.0139).Compared with other tumor markers,cf-dsDNA had higher diagnostic efficiency for PHC(AUC=0.965).According to the cut-off value(>1.912 ng/μL),the positive rate of cf-dsDNA in PHC was 90.32%(56/62),which was significantly higher than other tumor markers(χ^(2)=36.00,P<0.01).Conclusion:Plasma cf-dsDNA was a promising non-invasive marker for PHC diagnosis.