DNA methylation biomarkers discovered in silico detect cancer in liquid biopsies from non-small cell lung cancer patients

Epigenetics. 2020 Apr;15(4):419-430. doi: 10.1080/15592294.2019.1695333. Epub 2019 Nov 27.

Abstract

Identification of cancer-specific methylation of DNA released by tumours can be used for non-invasive diagnostics and monitoring. We previously reported in silico identification of DNA methylation loci specifically hypermethylated in common human cancers that could be used as epigenetic biomarkers. Using DNA methylation specific qPCR we now clinically tested a group of these cancer-specific loci on cell-free DNA (cfDNA) extracted from the plasma fraction of blood samples from healthy controls and non-small cell lung cancer (NSCLC) patients. These DNA methylation biomarkers distinguish lung cancer cases from controls with high sensitivity and specificity (AUC = 0.956), and furthermore, the signal from the markers correlates with tumour size and decreases after surgical resection of lung tumours. Presented observations suggest the clinical value of these DNA methylation biomarkers for NSCLC diagnostics and monitoring. Since we successfully validated the biomarkers using independent DNA methylation data from multiple additional common carcinoma cohorts (bladder, breast, colorectal, oesophageal, head and neck, pancreatic or prostate cancer) we predict that these DNA methylation biomarkers will detect additional carcinoma types from plasma samples as well.

Keywords: Cancer marker; DNA methylation; NSCLC; biomarker; cfDNA; liquid biopsy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / standards
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell-Free Nucleic Acids / blood
  • Cell-Free Nucleic Acids / genetics
  • Cell-Free Nucleic Acids / standards
  • DNA Methylation*
  • Female
  • Humans
  • Liquid Biopsy
  • Lung Neoplasms / blood
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids