Comprehensive Approach to Distinguish Patients with Solid Tumors from Healthy Controls by Combining Androgen Receptor Mutation p.H875Y with Cell-Free DNA Methylation and Circulating miRNAs

Elena Tomeva, Olivier Switzeny, Clemens Heitzinger, Berit Hippe, Alexander Haslberger (Corresponding author)

Publications: Contribution to journalArticlePeer Reviewed

Abstract

Liquid biopsy-based tests emerge progressively as an important tool for cancer diagnostics and management. Currently, researchers focus on a single biomarker type and one tumor entity. This study aimed to create a multi-analyte liquid biopsy test for the simultaneous detection of several solid cancers. For this purpose, we analyzed cell-free DNA (cfDNA) mutations and methylation, as well as circulating miRNAs (miRNAs) in plasma samples from 97 patients with cancer (20 bladder, 9 brain, 30 breast, 28 colorectal, 29 lung, 19 ovarian, 12 pancreas, 27 prostate, 23 stomach) and 15 healthy controls via real-time qPCR. Androgen receptor p.H875Y mutation (AR) was detected for the first time in bladder, lung, stomach, ovarian, brain, and pancreas cancer, all together in 51.3% of all cancer samples and in none of the healthy controls. A discriminant function model, comprising cfDNA mutations (COSM10758, COSM18561), cfDNA methylation markers (MLH1, MDR1, GATA5, SFN) and miRNAs (miR-17-5p, miR-20a-5p, miR-21-5p, miR-26a-5p, miR-27a-3p, miR-29c-3p, miR-92a-3p, miR-101-3p, miR-133a-3p, miR-148b-3p, miR-155-5p, miR-195-5p) could further classify healthy and tumor samples with 95.4% accuracy, 97.9% sensitivity, 80% specificity. This multi-analyte liquid biopsy-based test may help improve the simultaneous detection of several cancer types and underlines the importance of combining genetic and epigenetic biomarkers.
Original languageEnglish
Article number462
Number of pages14
JournalCancers
Volume14
Issue number2
DOIs
Publication statusPublished - Jan 2022

Austrian Fields of Science 2012

  • 304002 Genetic diagnostics

Keywords

  • CANCER
  • LIQUID BIOPSIES
  • PLASMA
  • RESISTANCE
  • SERUM
  • biomarker
  • cancer
  • cell-free DNA
  • classification
  • liquid-biopsy
  • methylation
  • microRNA
  • Biomarker
  • Liquid-biopsy
  • MicroRNA
  • Classification
  • Cell-free DNA
  • Methylation
  • Cancer

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