血浆游离DNA完整性指标在恶性甲状腺肿瘤中的诊断价值

Diagnostic value of plasma cell-free DNA integrity index in patients with malignancy thyroid nodule

目的探讨血浆中细胞游离DNA(cfDNA)浓度和cfDNA完整性指标作为一种非侵入性方法用于术前甲状腺癌诊断的作用。方法收集2017年2月至4月郑州大学第一附属医院甲状腺外一科收治的75例甲状腺肿瘤患者血浆,其中良性甲状腺瘤患者31例,恶性甲状腺瘤患者44例,用ALU-荧光定量聚合酶链反应(PCR)方法检测良恶性肿瘤患者血浆中cfDNA浓度和cfDNA完整性指标,并比较其在这两组中的差异。用受试者工作特征(ROC)曲线研究将血浆中cfDNA浓度和cfDNA完整性指标作为恶性甲状腺肿瘤诊断的可行性。分类资料的比较采用χ2检验。结果恶性甲状腺肿瘤患者血浆中以ALU115为引物定量的cfDNA总浓度为4132μg/L(1055~9372μg/L),良性组1491μg/L(387~3031μg/L);cfDNA完整性指标为0.65(0.56~0.83),良性组0.39(0.25~0.52);恶性组均显著高于良性组(P<0.01,P<0.01)。ROC曲线显示当联合超声检查和血浆cfDNA完整性指标对恶性肿瘤进行诊断时,其灵敏度、特异性、准确率、阳性预测值PPV和阴性预测值NPV分别为95.0%、94.0%、95.0%、89.4%和73.0%。均显著高于以超声、cfDNA总浓度和cfDNA完整性指数单独诊断。结论对于甲状腺肿瘤患者,应首先使用甲状腺超声检查,对于怀疑恶性甲状腺肿瘤的患者,血浆中cfDNA完整性指数有助于恶性甲状腺肿瘤的诊断,从而减少细针穿刺病理活检等有创检查。

Objective:To investigate the effect of plasma cell-free DNA(cfDNA)concentration or cfDNA integrity index used as a non-invasion method for thyroid cancer diagnosis.Methods:Plasma samples were collected from 75 patients with thyroid nodules in Department of Thyroid Surgery,the First Affiliated Hospital of Zhengzhou University from February to April,2017.We classified all patients into two groups:benign thyroid nodule group(n=31)and malignant thyroid nodule group(n=44).Plasma-cfDNA was quantified by ALU-based polymerase chain reaction(PCR).The concentration of cfDNA(ALU115)and cfDNA integrity index were compared between these two groups.Receiver operating characteristic(ROC)curve was performed to find a more useful diagnostic method for malignant thyroid nodule.Results:In malignant group,the cfDNA concentration(ALU115)was 4132μg/L(1055-9372μg/L)and cfDNA integrity index was 0.65(0.56-0.83),which were both significantly higher than those in benign thyroid nodule group.When compared the diagnosis ability using ultrasound,cfDNA concentration(ALU-115)and cfDNA integrity index,the results of ROC curve indicated that the combination of ultrasound with plasma-cfDNA integrity index was the most effective way to diagnose malignant thyroid nodule:95.0%sensitively,94.0%specificity,95.0%accuracy,89.4%PPV and 75.0%NPV.Conclusion:Ultrasound could be the first diagnosis method for patients with thyroid nodules.Plasma-cfDNA integrity index was a more useful way for malignant thyroid nodule diagnosis when suspicious malignant thyroid nodules were reported by ultrasound.In total,we suggest that the combination of ultrasound test and plasma-cfDNA integrity index is an non-invasion method for malignant thyroid nodule diagnosis.