Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hofmann, L; Sallinger, K; Haudum, C; Smolle, M; Heitzer, E; Moser, T; Novy, M; Gesson, K; Kroneis, T; Bauernhofer, T; El-Heliebi, A.
A Multi-Analyte Approach for Improved Sensitivity of Liquid Biopsies in Prostate Cancer.
Cancers (Basel). 2020; 12(8):
Doi: 10.3390/cancers12082247
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- Führende Autor*innen der Med Uni Graz
- Bonstingl Lilli
- El-Heliebi Amin
- Co-Autor*innen der Med Uni Graz
- Bauernhofer Thomas
- Haudum Christoph
- Heitzer Ellen
- Kroneis Thomas
- Moser Tina
- Sallinger Katja
- Smolle Maria Anna
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- Abstract:
- Novel androgen receptor (AR) signaling inhibitors have improved the treatment of castration-resistant prostate cancer (CRPC). Nonetheless, the effect of these drugs is often time-limited and eventually most patients become resistant due to various AR alterations. Although liquid biopsy approaches are powerful tools for early detection of such therapy resistances, most assays investigate only a single resistance mechanism. In combination with the typically low abundance of circulating biomarkers, liquid biopsy assays are therefore informative only in a subset of patients. In this pilot study, we aimed to increase overall sensitivity for tumor-related information by combining three liquid biopsy approaches into a multi-analyte approach. In a cohort of 19 CRPC patients, we (1) enumerated and characterized circulating tumor cells (CTCs) by mRNA-based in situ padlock probe analysis, (2) used RT-qPCR to detect cancer-associated transcripts (e.g., AR and AR-splice variant 7) in lysed whole blood, and (3) conducted shallow whole-genome plasma sequencing to detect AR amplification. Although 44-53% of patient samples were informative for each assay, a combination of all three approaches led to improved diagnostic sensitivity, providing tumor-related information in 89% of patients. Additionally, distinct resistance mechanisms co-occurred in two patients, further reinforcing the implementation of multi-analyte liquid biopsy approaches.
- Find related publications in this database (Keywords)
- CTCs
- prostate cancer
- AR-V7
- in situ padlock probe
- ARamplification
- liquid biopsy
- multi-analyte