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

Autor(en)

Elena Tomeva, Olivier Switzeny, Clemens Heitzinger, Berit Hippe, Alexander Haslberger

Abstrakt

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,mMDR1, 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 severalcancer types and underlines the importance of combining genetic and epigenetic biomarkers

Organisation(en)

Department für Ernährungswissenschaften

Externe Organisation(en)

Technische Universität Wien, HealthBioCare GmbH

Journal

Cancers

Band

14

Anzahl der Seiten

14

ISSN

2072-6694

DOI

https://doi.org/10.3390/cancers14020462

Publikationsdatum

01-2022

Peer-reviewed

Ja

ÖFOS 2012

304002 Genetische Diagnostik

Schlagwörter

ASJC Scopus Sachgebiete

Oncology, Cancer Research

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/comprehensive-approach-to-distinguish-patients-with-solid-tumors-from-healthy-controls-by-combining-androgen-receptor-mutation-ph875y-with-cellfree-dna-methylation-and-circulating-mirnas(fdeece59-50ae-4ecf-8f15-6baabf0b9359).html