Direct plasmonic detection of circulating RAS mutated DNA in colorectal cancer patients

Roberta D'Agata, Noemi Bellassai, Matteo Allegretti, Andrea Rozzi, Saša Korom, Alex Manicardi, Elisa Melucci, Edoardo Pescarmona, Roberto Corradini, Patrizio Giacomini, Giuseppe Spoto

Research output: Contribution to journalArticlepeer-review

Abstract

RAS mutations in the blood of colorectal cancer (CRC) patients are emerging as biomarkers of acquired resistance to Epidermal Growth Factor Receptor therapy. Unfortunately, reliable assays granting fast, real-time monitoring of treatment response, capable of refining retrospective, tissue-based analysis, are still needed. Recently, several methods for detecting blood RAS mutations have been proposed, generally relying on multi-step and PCR-based, time-consuming and cost-ineffective procedures. By exploiting a liquid biopsy approach, we developed an ultrasensitive nanoparticle-enhanced plasmonic method for detecting ~1 aM RAS single nucleotide variants (SNVs) in the plasma of CRC patients. The assay does not require the extraction of tumor DNA from plasma and detects it in volumes as low as 40 μL of plasma, which is at least an order of magnitude smaller than that required by state of the art liquid biopsy technologies. The most prevalent RAS mutations are detected in DNA from tumor tissue with 100% sensitivity and 83.33% specificity. Spike-in experiments in human plasma further encouraged assay application on clinical specimens. The assay was proven in plasma from CRC patients and healthy donors, and full discrimination between mutated DNA from patients over wild-type DNA from healthy volunteers was obtained thus demonstrating its promising avenue for cancer monitoring based on liquid biopsy.

Original languageEnglish
Article number112648
JournalBiosensors and Bioelectronics
Volume170
DOIs
Publication statusPublished - Dec 15 2020

Keywords

  • Colorectal cancer
  • Gold nanoparticles
  • Liquid biopsy
  • Plasmonics
  • RAS mutations

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Biomedical Engineering
  • Electrochemistry

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