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

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

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.

Keywords: Circulating tumour DNA; K-ras mutation; Prognostic value; Ultrasensitive detection method.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • DNA, Neoplasm / blood
  • DNA, Neoplasm / isolation & purification*
  • Female
  • Genes, ras
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Polymerase Chain Reaction / methods*
  • Prognosis
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm