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Article

A Multi-Analyte Approach for Improved Sensitivity of Liquid Biopsies in Prostate Cancer

1
Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria
2
Center for Biomarker Research in Medicine (CBmed), 8010 Graz, Austria
3
Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, 8010 Graz, Austria
4
Department of Orthopaedics and Trauma, Medical University of Graz, 8010 Graz, Austria
5
Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, 8010 Graz, Austria
6
BioTechMed-Graz, 8010 Graz, Austria
7
Christian Doppler Laboratory for Liquid Biopsies for Early Detection of Cancer, Medical University of Graz, 8010 Graz, Austria
8
ViennaLab Diagnostics, 1120 Vienna, Austria
9
Division of Oncology, Department of Internal Medicine, Medical University of Graz, 8010 Graz, Austria
*
Author to whom correspondence should be addressed.
Co-senior authorship.
Cancers 2020, 12(8), 2247; https://doi.org/10.3390/cancers12082247
Received: 15 May 2020 / Revised: 7 August 2020 / Accepted: 9 August 2020 / Published: 11 August 2020
(This article belongs to the Special Issue Circulating Tumor Cells' Heterogeneity and Precision Oncology)
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. View Full-Text
Keywords: CTCs; prostate cancer; AR-V7; in situ padlock probe; AR amplification; liquid biopsy; multi-analyte CTCs; prostate cancer; AR-V7; in situ padlock probe; AR amplification; liquid biopsy; multi-analyte
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MDPI and ACS Style

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 2020, 12, 2247. https://doi.org/10.3390/cancers12082247

AMA Style

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. 2020; 12(8):2247. https://doi.org/10.3390/cancers12082247

Chicago/Turabian Style

Hofmann, Lilli, Katja Sallinger, Christoph Haudum, Maria Smolle, Ellen Heitzer, Tina Moser, Michael Novy, Kevin Gesson, Thomas Kroneis, Thomas Bauernhofer, and Amin El-Heliebi. 2020. "A Multi-Analyte Approach for Improved Sensitivity of Liquid Biopsies in Prostate Cancer" Cancers 12, no. 8: 2247. https://doi.org/10.3390/cancers12082247

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