Comparative study of droplet-digital PCR and absolute Q digital PCR for ctDNA detection in early-stage breast cancer patients

Clin Chim Acta. 2024 Jan 1:552:117673. doi: 10.1016/j.cca.2023.117673. Epub 2023 Nov 23.

Abstract

Background: Analysis of circulating tumor DNA (ctDNA) is increasingly used for clinical decision-making in oncology. However, ctDNA could represent ≤ 0.1 % of cell-free DNA in early-stage tumors and its detection requires high-sensitive techniques such as digital PCR (dPCR).

Methods: In 46 samples from patients with early-stage breast cancer, we compared two leading dPCR assays for ctDNA analysis: QX200 droplet digital PCR (ddPCR) system from Bio-Rad which is the gold-standard in the field, and Absolute Q plate-based digital PCR (pdPCR) system from Thermo Fisher Scientific which has not been reported before. We analyzed 5 mL of baseline plasma samples prior to any treatment.

Results: Both systems displayed a comparable sensitivity with no significant differences observed in mutant allele frequency. In fact, ddPCR and pdPCR possessed a concordance > 90 % in ctDNA positivity. Nevertheless, ddPCR exhibited higher variability and a longer workflow. Finally, we explored the association between ctDNA levels and clinicopathological features. Significantly higher ctDNA levels were present in patients with a Ki67 score > 20 % or with estrogen receptor-negative or triple-negative breast cancer subtypes.

Conclusion: Both ddPCR and pdPCR may constitute sensitive and reliable tools for ctDNA analysis with an adequate agreement in early-stage breast cancer patients.

Keywords: Breast cancer; Circulating tumor DNA; Digital PCR; Liquid biopsy.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Cell-Free Nucleic Acids*
  • Circulating Tumor DNA* / genetics
  • Humans
  • Mutation
  • Polymerase Chain Reaction / methods
  • Triple Negative Breast Neoplasms*

Substances

  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • Circulating Tumor DNA