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- Title
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.
- Authors
Tomeva, Elena; Switzeny, Olivier J.; Heitzinger, Clemens; Hippe, Berit; Haslberger, Alexander G.
- Abstract
Simple Summary: Blood-based tests for cancer detection are minimally invasive and could be useful for screening asymptomatic patients and high-risk populations. Since a single molecular biomarker is usually insufficient for an accurate diagnosis, we developed a multi-analyte liquid biopsy-based classification model to distinguish cancer patients from healthy subjects. The combination of cell-free DNA mutations, miRNAs, and cell-free DNA methylation markers improved the model's performance. Moreover, we demonstrated that the androgen receptor mutation p.H875Y is not only relevant in prostate cancer but had a strong predictive value for colorectal, bladder, and breast cancer. Our results, although preliminary, showed that a single liquid biopsy test could detect multiple cancer types simultaneously. 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.
- Subjects
NUCLEIC acid analysis; TUMOR diagnosis; BLADDER tumors; PANCREATIC tumors; STOMACH tumors; GENETIC mutation; BIOPSY; OVARIAN tumors; MICRORNA; LUNG tumors; DNA methylation; CANCER patients; BRAIN tumors; COLORECTAL cancer; DESCRIPTIVE statistics; ANDROGEN receptors; EXTRACELLULAR space; POLYMERASE chain reaction; TUMOR markers; BREAST tumors; PROSTATE tumors
- Publication
Cancers, 2022, Vol 14, Issue 2, p462
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers14020462