Validation of Cell-Free RNA and Circulating Tumor Cells for Molecular Marker Analysis in Metastatic Prostate Cancer.

Michael Ladurner,Jasmin Bektic,Manuel Wieser,Wolfgang Horninger,Iris E Eder,Gabriele Dobler,Martin Seewald,Helmut Klocker,Isabel Heidegger,Peter Obrist,Mona Kafka,Hannes Neuwirt,Andrea Eigentler

doi:10.3390/biomedicines9081004

Michael Ladurner, Jasmin Bektic + Show 11 more

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https://doi.org/10.3390/biomedicines9081004

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Abstract

Since tissue material is often lacking in metastatic prostate cancer (mPCa), there is increasing interest in using liquid biopsies for treatment decision and monitoring therapy responses. The purpose of this study was to validate the usefulness of circulating tumor cells (CTCs) and plasma-derived cell-free (cf) RNA as starting material for gene expression analysis through qPCR. CTCs were identified upon prostate-specific membrane antigen and/or cytokeratin positivity after enrichment with ScreenCell (Westford, Massachusetts, USA) filters or the microfluidic ParsortixTM (Guildford, Surrey, United Kingdom) system. Overall, 50% (28/56) of the patients had ≥5 CTCs/7.5 mL of blood. However, CTC count did not correlate with Gleason score, serum PSA, or gene expression. Notably, we observed high expression of CD45 in CTC samples after enrichment, which could be successfully eliminated through picking of single cells. Gene expression in picked CTCs was, however, rather low. In cfRNA from plasma, on the other hand, gene expression levels were higher compared to those found in CTCs. Moreover, we found that PSA was significantly increased in plasma-derived cfRNA of mPCa patients compared to healthy controls. High PSA expression was also associated with poor overall survival, indicating that using cfRNA from plasma could be used as a valuable tool for molecular expression analysis.

Highlights

Introduction published maps and institutional affilProstate cancer (PCa) is the most frequent male cancer in Western societies followed by lung and colon cancer [1]
We determined the circulating tumor cells (CTCs) count in 56 blood samples from 41 patients with metastatic prostate cancer (mPCa) diagnosed through imaging
Our study focused on the expression of a limited gene panel by Quantitative RT-PCR (qPCR) in an unselected, very heterogeneous cohort of patient samples, similar to that with which clinicians are confronted in their routine work

Summary

Introduction

Introduction published maps and institutional affilProstate cancer (PCa) is the most frequent male cancer in Western societies followed by lung and colon cancer [1]. Because of the strong relevance of androgens, androgen deprivation therapy (ADT) is a mainstay in the treatment of metastatic prostate cancer (mPCa). Progression to castration-resistant prostate cancer (CRPC) eventually occurs in most patients [3]. MPCa is not curable; the number of available therapies to slow tumor progression significantly increased in the past few years, including chemotherapy even in earlier hormone-sensitive settings, anti-androgenic drug abiraterone [4], androgen receptor inhibitors like enzalutamide, apalutamide and darolutamide [5,6,7], and radium-223 [8]. Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors have been approved for the treatment of metastatic CRPC (mCRPC) but were limited to use in patients with verified iations

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