Eskandari Mahsa, Manoochehrabadi Saba, Pashaiefar Hossein, Zaimy Mohammad Ali, Ahmadvand Mohammad
Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Medical Genetics, Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Blood Res. 2019 Jun;54(2):114-119. doi: 10.5045/br.2019.54.2.114. Epub 2019 Jun 25.
Cell-free DNA (cfDNA) has the potential to serve as a non-invasive prognostic biomarker in some types of neoplasia. The investigation of plasma concentration of cfDNA may reveal its use as a valuable biomarker for risk stratification of diffuse large B-cell lymphoma (DLBCL). The present prognostic value of plasma cfDNA has not been widely confirmed in DLBCL subjects. Here, we evaluated cfDNA plasma concentration and assessed its potential prognostic value as an early DLBCL diagnostic tool.
cfDNA concentrations in plasma samples from 40 patients with DLBCL during diagnosis and of 38 normal controls were determined with quantitative polymerase chain reaction (qPCR) for the multi-locus gene.
Statistically significant elevation in plasma cfDNA concentrations was observed in patients with DLBCL as compared to that in normal controls (<0.05). A cutoff point of 2.071 ng/mL provided 82.5% sensitivity and 62.8% specificity and allowed successful discrimination of patients with DLBCL from normal controls (area under the curve=0.777; =0.00003). Furthermore, patients with DLBCL showing higher concentrations of cfDNA had shorter overall survival (median, 9 mo; =0.022) than those with lower cfDNA levels. In addition, elevated cfDNA concentration was significantly associated with age, B-symptoms, International Prognostic Index (IPI) score, and different stages of disease (all <0.05).
Quantification of cfDNA with qPCR at the time of diagnosis may allow identification of patients with high cfDNA concentration, which correlates with aggressive clinical outcomes and adverse prognosis.
游离DNA(cfDNA)有潜力作为某些类型肿瘤的非侵入性预后生物标志物。对cfDNA血浆浓度的研究可能揭示其作为弥漫性大B细胞淋巴瘤(DLBCL)风险分层的有价值生物标志物的用途。血浆cfDNA目前的预后价值在DLBCL患者中尚未得到广泛证实。在此,我们评估了血浆cfDNA浓度,并评估了其作为早期DLBCL诊断工具的潜在预后价值。
采用定量聚合酶链反应(qPCR)对多位点基因测定40例DLBCL患者诊断时血浆样本及38例正常对照的cfDNA浓度。
与正常对照相比,DLBCL患者血浆cfDNA浓度有统计学显著升高(<0.05)。截断点为2.071 ng/mL时,灵敏度为82.5%,特异性为62.8%,能够成功区分DLBCL患者与正常对照(曲线下面积=0.777;=0.00003)。此外,cfDNA浓度较高的DLBCL患者总生存期较短(中位数为9个月;=0.022),低于cfDNA水平较低的患者。此外,cfDNA浓度升高与年龄、B症状、国际预后指数(IPI)评分及疾病不同分期均显著相关(均<0.05)。
诊断时用qPCR对cfDNA进行定量,可能有助于识别cfDNA浓度高的患者,这与侵袭性临床结果和不良预后相关。