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循环游离 DNA 浓度是肺癌的独立预后生物标志物。

Circulating free DNA concentration is an independent prognostic biomarker in lung cancer.

机构信息

Department of Acute Respiratory Medicine and Thoracic Oncology Department, Lyon Sud Hospital and Lyon University Cancer Institute, Lyon University Hospital, Pierre Bénite, France International Agency for Research on Cancer, Molecular Mechanisms and Biomarkers Group, Lyon, France.

Université Grenoble 1, INSERM, U 823, Institut A Bonniot, Université J Fourier, La Tronche, France Thoracic Oncology Unit, Teaching Hospital A Michallon, Grenoble, France.

出版信息

Eur Respir J. 2015 Dec;46(6):1773-80. doi: 10.1183/13993003.00676-2015. Epub 2015 Oct 22.

Abstract

Plasma circulating cell-free (cf)DNA is of interest in oncology because it has been shown to contain tumour DNA and may thus be used as liquid biopsy. In nonsmall cell lung cancer (NSCLC), cfDNA quantification has been proposed for the monitoring and follow-up of patients. However, available studies are limited and need to be confirmed by studies with larger sample sizes and including patients who receive more homogenous treatments. Our objective was to assess the predictive and prognostic value of plasma cfDNA concentration in a large series of patients with NSCLC and treated with a standard chemotherapy regimen.We included samples from lung cancer patients recruited into the Pharmacogenoscan study. The cfDNA of 218 patients was extracted and quantified by fluorometry before and after two or three cycles of platinum-based chemotherapy. The association between baseline and post-chemotherapy concentrations and treatment response, assessed by RECIST (response evaluation criteria in solid tumours) or patient survival was analysed.Patients with high cfDNA concentrations (highest tertile) at baseline had a significantly worse disease-free and overall survival than those with lower concentrations (lowest and middle tertiles) (median overall survival 10 months (95% CI 10.7-13.9) versus 14.2 months (95% CI 12.6-15.8), respectively; p=0.001). In multivariate analysis, increased baseline concentration of cfDNA was an independent prognostic factor. However, we did not find any association between cfDNA concentration and response to treatment.cfDNA may be a biomarker for the assessment of prognosis in NSCLC. However, total concentration of cfDNA does not appear to predict chemotherapy response.

摘要

血浆循环无细胞(cf)DNA 在肿瘤学中很有研究意义,因为它已被证明含有肿瘤 DNA,因此可用作液体活检。在非小细胞肺癌(NSCLC)中,cfDNA 定量已被提出用于监测和随访患者。然而,现有研究有限,需要通过更大样本量的研究和包括接受更同质治疗的患者来证实。我们的目的是评估 NSCLC 患者血浆 cfDNA 浓度在一系列患者中的预测和预后价值,并接受标准化疗方案治疗。我们纳入了 Pharmacogenoscan 研究中招募的肺癌患者的样本。在铂类化疗两或三个周期前后,通过荧光法提取和定量 218 例患者的 cfDNA。通过 RECIST(实体瘤反应评估标准)或患者生存分析评估基线和化疗后浓度与治疗反应之间的相关性。基线时 cfDNA 浓度较高(最高三分位)的患者无病和总生存明显较差,低于较低浓度(最低和中间三分位)的患者(中位总生存时间 10 个月(95%CI 10.7-13.9)与 14.2 个月(95%CI 12.6-15.8)相比;p=0.001)。多变量分析表明,cfDNA 基线浓度增加是独立的预后因素。然而,我们没有发现 cfDNA 浓度与治疗反应之间存在任何关联。cfDNA 可能是 NSCLC 评估预后的生物标志物。然而,cfDNA 的总浓度似乎不能预测化疗反应。

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