Related Experiment Video
Updated: Dec 11, 2025
Author Spotlight: Advancing Prostate Cancer Research Through Improved Tissue Sampling and Biobanking
Published on: November 17, 2023
A Multi-Analyte Approach for Improved Sensitivity of Liquid Biopsies in Prostate Cancer
Lilli Hofmann1,2, Katja Sallinger1,2, Christoph Haudum2,3
1Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria.
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.
Insights
Combining three liquid biopsy methods significantly improves detection of resistance mechanisms in castration-resistant prostate cancer (CRPC) patients. This multi-analyte approach provides crucial tumor information in 89% of patients, enhancing treatment monitoring.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Novel androgen receptor (AR) signaling inhibitors offer improved treatment for castration-resistant prostate cancer (CRPC).
- Therapeutic efficacy is often limited by acquired resistance, frequently driven by AR alterations.
- Current liquid biopsy assays often focus on single resistance mechanisms, limiting their sensitivity.
Purpose of the Study:
- To enhance the sensitivity of liquid biopsy for detecting tumor-related information in CRPC patients.
- To develop and evaluate a multi-analyte liquid biopsy approach by combining three distinct methods.
- To assess the diagnostic yield of a combined approach in a cohort of CRPC patients.
Main Methods:
- Enumeration and characterization of circulating tumor cells (CTCs) using mRNA-based in situ padlock probe analysis.
- Detection of cancer-associated transcripts, including AR and AR-splice variant 7, via RT-qPCR in whole blood.
- Shallow whole-genome sequencing of plasma to identify AR amplification.
Main Results:
- Each individual assay provided informative results for 44-53% of patient samples.
- The combined multi-analyte approach yielded tumor-related information in 89% of CRPC patients.
- Co-occurrence of distinct resistance mechanisms was observed in two patients.
Conclusions:
- A multi-analyte liquid biopsy strategy significantly increases diagnostic sensitivity for detecting resistance mechanisms in CRPC.
- This integrated approach provides comprehensive tumor information, improving patient monitoring and potential therapeutic guidance.
- The findings support the clinical implementation of multi-analyte liquid biopsies for managing CRPC.
More Related Videos
08:08Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
13:19Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013