定量检测血浆DNA水平评估非小细胞肺癌患者术后复发的价值

Correlation of plasma DNA level to recurrence in surgical patients with non-small cell lung cancer

目的探讨定量检测非小细胞肺癌（NSCLC）患者手术前后的血浆DNA水平对术后复发的预测能力。方法采集做肺癌根治术的40名NSCLC患者术前2～14d（中住天数：6d）及术后5～16d（中位天数：8d）的静脉血，采用含内参照双重荧光定量PCR技术，进行血浆DNA定量检测。结果血浆DNA含量在100名健康对照者为18．5（15．5～24．9）ng／ml，在NSCLC患者术前为66．5（49．4—76．4）ng／ml，术后为56．9（43．1～89．6）ng／ml，均显著高于健康对照组（P〈0．001）。29例未复发患者，术后血浆DNA水平显著降低（P〈0．001），11例复发患者手术前后DNA水平无显著差异（P=0．131）。血浆DNA定量对NSCLC患者术后复发的诊断效能，在术前AUC：0．448，术后AUC：0．868，术后显著优于术前（P=0．002）。以术后血浆DNA≥73．3ng／ml作为临界值，预测复发的敏感性：81．8％，特异性：82．8％，阳性预测值：64．3％，阴性预测值192．3％。结论术后1—2周测定血浆DNA可对NSCLC患者术后复发进行评估，远早于常用的检查技术，具有重要的临床应用价值。

Objective To explore the predictive value of plasma DNA quantitation for recurrence in surgical patients with non-small cell lung cancer （NSCLC）. Methods Plasma specimens were collected from 40 consecutive NSCLC patients before （median,6 days,2-14） and after surgery （median, 8 days, 5 -16）, as well as from 100 cancer-free controls. All cell-free plasma DNA was measured by quantitative duplex PCR with internal control. Patients were followed up at the 6th month after surgery by CT scanning and other examinations for evaluating the recurrence. Results Plasma DNA levels in NSCLC patients were 66.5 （49.4 - 76.4） ng/ml before surgery and 56.9 （43.1 - 89.6） ng/ml after surgery, presenting reduction in non-recurrences and unchanging in recurrences, which were beth higher than 18.5 （ 15.5 - 24.9） ng/ml of healthy controls （ P 〈 0.001 ）. The plasma DNA level was the only factor that correlated with recurrence after surgery, while other clinical and pathological factors were not. Plasma DNA quantitation of post-surgery （AUC = 0.868 ） was favorable to that of pre-surgery （ AUC = 0.448 ） for predicting 6-month recurrence, which presented positive predictive value of 64.3% and negative predictive value of 92.3% by selecting ≥73.3 ng/ml of postoperative plasma DNA （ sensitivity： 81.8%, specificity：82.8 % ） as cut-off value. Conclusions Plasma DNA quantitation at 1 -2 weeks after operation is useful prognostic biomarker for recurrence in NSCLC patients, which is applicable in clinical settings for the management of NSCLC patients prior to elinieal findings.