基于芯片的数字PCR平台在检测转移性结直肠癌循环DNA中的临床价值

Clinical value of chip-based digital-PCR platform for the detection of circulating DNA in metastatic colorectal cancer.

作者信息

Sefrioui David, Sarafan-Vasseur Nasrin, Beaussire Ludivine, Baretti Marina, Gangloff Alice, Blanchard France, Clatot Florian, Sabourin Jean-Christophe, Sesboüé Richard, Frebourg Thierry, Michel Pierre, Di Fiore Frédéric

机构信息

Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen Cedex, France; EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France.

EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France.

出版信息

Dig Liver Dis. 2015 Oct;47(10):884-90. doi: 10.1016/j.dld.2015.05.023. Epub 2015 Jun 5.

DOI:10.1016/j.dld.2015.05.023

PMID:26160500

Abstract

BACKGROUND

The detection of circulating DNA is considered a promising strategy in cancer patients. Digital PCR has emerged as a sensitive method able to quantify both circulating free and tumour DNA.

AIM

The aim of this study was to prospectively evaluate the clinical value of a chip-based digital PCR for the detection of circulating DNA.

METHODS

Digital PCR was used in 34 metastatic colorectal cancer patients to detect and quantify circulating free and tumour DNA based on K-ras mutational status. Clinical outcomes were analyzed according to circulating DNA measurements.

RESULTS

Digital PCR yielded a detection rate of 69% for circulating tumour DNA. The median concentrations of circulating free and tumour DNA were 20 and 6.8 ng/mL, respectively, with significant correlation between both biomarkers (p<0.001). Median overall survival was 4.8 months in patients with high circulating free DNA (>75% quartile) versus not reached in patients with a low level (<25% quartile) (p=0.029). Moreover, median overall survival was significantly decreased in patients with detectable circulating tumour DNA compared to those without (respectively 11.8 months versus not reached, p=0.04).

CONCLUSIONS

Chip-based digital PCR is a simple and non-invasive method allowing the efficient detection of circulating DNA. Our results highlight that levels of these circulating markers may have a potential prognostic value.

摘要

背景

循环DNA的检测被认为是癌症患者一种有前景的策略。数字PCR已成为一种能够对循环游离DNA和肿瘤DNA进行定量的灵敏方法。

目的

本研究的目的是前瞻性评估基于芯片的数字PCR检测循环DNA的临床价值。

方法

对34例转移性结直肠癌患者使用数字PCR，基于K-ras突变状态检测和定量循环游离DNA和肿瘤DNA。根据循环DNA测量结果分析临床结局。

结果

数字PCR检测循环肿瘤DNA的检出率为69%。循环游离DNA和肿瘤DNA的中位浓度分别为20 ng/mL和6.8 ng/mL，两种生物标志物之间存在显著相关性（p<0.001）。循环游离DNA水平高（>四分位数75%）的患者中位总生存期为4.8个月，而水平低（<四分位数25%）的患者未达到（p=0.029）。此外，与未检测到循环肿瘤DNA的患者相比，检测到循环肿瘤DNA的患者中位总生存期显著缩短（分别为11.8个月和未达到，p=0.04）。