Paci Massimiliano, Maramotti Sally, Bellesia Enrica, Formisano Debora, Albertazzi Laura, Ricchetti Tommaso, Ferrari Guglielmo, Annessi Valerio, Lasagni Daniela, Carbonelli Cristiano, De Franco Salvatore, Brini Maria, Sgarbi Giorgio, Lodi Renzo
Division of Thoracic Surgery, Azienda Ospedaliera Santa Maria Nuova, Viale Risorgimento 80, 42100 Reggio Emilia, Italy.
Lung Cancer. 2009 Apr;64(1):92-7. doi: 10.1016/j.lungcan.2008.07.012. Epub 2008 Sep 19.
The presence of circulating DNA in plasma of patients with malignant neoplasm has been a known fact for over 30 years. Since then, the concentration of free circulating plasma DNA has been studied as well as the genetic alterations and epigenetic alterations of tumour DNA of patients that suffer from various types of tumours. The analysis of circulating plasma DNA may be a useful marker to get an early diagnosis on malignant neoplasms. This study has been specifically designed to validate the quantification of circulating DNA in order to design a test useful for the early identification of non-small cell lung cancer patients and the monitoring of lung cancer progression. A second aim of this work is the sensibility and specificity evaluation of such method for future applications.
The quantity of plasma DNA was determined using quantitative Real-Time PCR with amplification of the human telomerase reverse transcriptase (hTERT) gene in 151 patients that suffer from lung cancer and 79 healthy controls. The performance of the test was evaluated with a ROC curve. The relationship between the DNA concentration and main demographic, clinical and pathological variables was examined with logistic regression models as well as multiple linear regression models.
The concentration of circulating plasma DNA was about four times higher in patients with lung cancer with respect to the controls (12.8 vs 2.9 ng/mL). The area under the ROC curve was 0.79 (95% CI, 0.710-0.83). The concentration of circulating DNA proved to be an important risk factor for the presence of the illness and a prognostic index in the follow-up.
The use of quantitative Real-Time PCR revealed that higher values of circulating DNA can be found in patients with lung neoplasm compared to the healthy controls. This could have practical implications such as the use in screening programs and a possible prognostic significance in the follow-up.
恶性肿瘤患者血浆中存在循环DNA这一事实已被知晓30多年。从那时起，人们对游离循环血浆DNA的浓度以及患有各种类型肿瘤患者的肿瘤DNA的基因改变和表观遗传改变进行了研究。循环血浆DNA分析可能是恶性肿瘤早期诊断的有用标志物。本研究专门设计用于验证循环DNA的定量，以设计一种有助于早期识别非小细胞肺癌患者和监测肺癌进展的检测方法。这项工作的第二个目的是评估该方法在未来应用中的敏感性和特异性。
使用定量实时PCR扩增人端粒酶逆转录酶（hTERT）基因，测定151例肺癌患者和79例健康对照者血浆DNA的量。用ROC曲线评估检测性能。用逻辑回归模型和多元线性回归模型检验DNA浓度与主要人口统计学、临床和病理变量之间的关系。
肺癌患者循环血浆DNA浓度比对照组高约四倍（12.8对2.9 ng/mL）。ROC曲线下面积为0.79（95%CI，0.710 - 0.83）。循环DNA浓度被证明是疾病存在的重要危险因素和随访中的预后指标。
定量实时PCR的应用表明，与健康对照相比，肺癌患者循环DNA值更高。这可能具有实际意义，如用于筛查项目以及在随访中可能具有预后意义。
