食管癌患者血浆循环DNA定量检测及临床特征分析

The clinical significance of plasma DNA quantification in patients with esophageal cancer

目的检测食管癌患者血浆循环DNA的含量并探讨其与临床病理特征之间的关系。方法采集44例食管癌患者及100例健康对照的外周血，用磁珠法提取DNA、双重实时荧光定量PCR检测血浆DNA含量，并用放免法检测血清CEA水平。结果食管癌患者血浆DNA含量（中位数：54．0ng／ml，四分位数区间：38．0—68．1ng／ml）显著高于健康对照（中位数：18．5ng／ml．四分位区间：15．5～24．9．g／ml），P〈0．001。Ⅱa期、Ⅱb期和Ⅲ～Ⅳ期患者血浆DNA含量分别37．0（27．2—46．2）ng／ml、53．0（41．4。63．7）ng／ml和66．3（55．9～81．8）ng／ml。Ⅲ～Ⅳ期明显高于Ⅱa～Ⅱb期（P=0．003）。Ⅱa和Ⅱb期组的血浆DNA含量显著高于健康对照组（P〈0．001）。高、中分化组和低分化组的血浆DNA含量分别为32．3（24．2～55．1）ng／ml、52．9（42．5—69．6）ng／ml和65．0（57．7～88．6）ng／ml，低分化组显著高于高、中分化组（P：0．010）。以32．3ng／mL作为临界值，血浆DNA诊断敏感性为91．2％，特异性为90．O％，ROC曲线下面积为0．959（95％Cl0．915～1．000），优于血清CEA。结论检测血浆DNA对食管癌的筛查、早期诊断、判断肿瘤侵袭与转移具有重要价值。

Objectives The aim of this study was to quantify the cell-free DNA in plasmas from patients with esophageal cancer and to correlate the results with the clinical-pathological parameters. Methods DNA was extracted from the plasmas of 44 patients with esophageal cancer and of 100 healthy controls with the BILATEST DNA Kit. The quantity of plasma DNA was determined using duplex realtime quantitative PCR. The performance of the test was evaluated with a ROC curve. Careinoembryonic antigen （CEA） was determined by radioimmunoassay. The relationships between the DNA concentration and main demographic, clinical and pathological variables were examined. Results The median concentration of the plasma DNA in the cancer group was significandy higher than that in the control [ 54.0 ng/mL vs 18.5 ng/mL, P 〈 0.001 ; interquartile range, （ 38.0 - 68.1 ） ng/mL vs （ 15.5 - 24.9 ） ng/mL ]. Plasma DNA concentration was closely associated with the clinical stage （P = 0.003 ） and differentiation （P = 0.010） in esophageal cancer. The plasma DNA tended to increase in advanced stage and poor differentiation. A plasma DNA concentration of 32.3 ng/mL was considered as the cut-off value to achieve the best sensitivity （91.2%） and specificity （90.0%） for esophageal cancer. Quantification of plasma DNA was more sensitive than CEA in detecting esophageal cancer （91.2% vs 5.9% ）. Conclusions Plasma DNA level in the esophageal cancer patient is significantly higher than that in healthy control. Quantification of plasma DNA is valuable in screening, early diagnosing, and monitoring progression of esophageal cancer.