scholarly journals Prognostic Significance of Gene Expression and DNA Methylation Markers in Circulating Tumor Cells and Paired Plasma Derived Exosomes in Metastatic Castration Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 780
Author(s):  
Martha Zavridou ◽  
Areti Strati ◽  
Evangelos Bournakis ◽  
Stavroula Smilkou ◽  
Victoria Tserpeli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Dna Methylation ◽  
Tumor Cells ◽  
Liquid Biopsy ◽  
Prognostic Significance ◽  
Comparison Study ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
First Time

Liquid biopsy, based on the analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), provides non-invasive real-time monitoring of tumor evolution and therapeutic efficacy. We performed for the first time a direct comparison study on gene expression and DNA methylation markers in CTCs and paired plasma-derived exosomes and evaluated their prognostic significance in metastatic castration resistant prostate cancer. This prospective liquid biopsy (LB) study was based on a group of 62 metastatic castration resistant prostate cancer (mCRPC) patients and 10 healthy donors (HD) as controls. Identical blood draws were used to: (a) enumerate CTC and tumor-derived extracellular vesicles (tdEVs) using CellSearch (CS) and (b) analyze CTCs and paired plasma-derived exosomes at the gene expression and DNA methylation level. CTCs were enumerated using CellSearch in 57/62 patients, with values ranging from 5 to 854 cells/7.5 mL PB. Our results revealed for the first time a significantly higher positivity of gene expression markers (CK-8, CK-18, TWIST1, PSMA, AR-FL, AR-V7, AR-567 and PD-L1 mRNA) in EpCAM-positive CTCs compared to plasma-derived exosomes. GSTP1, RASSF1A and SCHLAFEN were methylated both in CTC and exosomes. In CTCs, Kaplan–Meier analysis revealed that CK-19 (p = 0.009), PSMA (p = 0.001), TWIST1 (p = 0.001) expression and GSTP1 (p = 0.001) methylation were correlated with OS, while in exosomes GSTP1 (p = 0.007) and RASSF1A (p = 0.001) methylation was correlated with OS. Our direct comparison study of CTCs and exosomes at gene expression and DNA methylation level, revealed for the first time a significantly higher positivity in EpCAM-positive CTCs compared to plasma-derived exosomes. Future perspective of this study should be the evaluation of clinical utility of molecular biomarkers in CTCs and exosomes on independent multicentric cohorts with mCRPC patients.

scholarly journals Gene Expression Alterations during Development of Castration-Resistant Prostate Cancer Are Detected in Circulating Tumor Cells

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 39 ◽  
Author(s):  
Andreas Josefsson ◽  
Karin Larsson ◽  
Eva Freyhult ◽  
Jan-Erik Damber ◽  
Karin Welén
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Progression ◽  
Expression Patterns ◽  
Therapy Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Cancer Specific Survival ◽  
Castration Resistant

Development of castration-resistant prostate cancer (CRPC) is associated with alterations in gene expression involved in steroidogenesis and androgen signaling. This study investigates whether gene expression changes related to CRPC development can be identified in circulating tumor cells (CTCs). Gene expression in paired CTC samples from 29 patients, before androgen deprivation therapy (ADT) and at CRPC relapse, was compared using a panel including 47 genes related to prostate cancer progression on a qPCR platform. Fourteen genes displayed significantly changed gene expression in CTCs at CRPC relapse compared to before start of ADT. The genes with increased expression at CRPC relapse were related to steroidogenesis, AR-signaling, and anti-apoptosis. In contrast, expression of prostate markers was downregulated at CRPC. We also show that midkine (MDK) expression in CTCs from metastatic hormone-sensitive prostate cancer (mHSPC) was associated to short cancer-specific survival (CSS). In conclusion, this study shows that gene expression patterns in CTCs reflect the development of CRPC, and that MDK expression levels in CTCs are prognostic for cancer-specific survival in mHSPC. This study emphasizes the role of CTCs in exploring mechanisms of therapy resistance, as well as a promising biomarker for prognostic and treatment-predictive purposes in advanced mHSPC.

scholarly journals Circulating Tumor Cells in Prostate Cancer: From Discovery to Clinical Utility

2019 ◽  
Vol 65 (1) ◽  
pp. 87-99 ◽  
Author(s):  
Klaus Pantel ◽  
Claudia Hille ◽  
Howard I Scher
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Medical Decision ◽  
Cancer Type ◽  
Castration Resistant Prostate Cancer ◽  
The Past ◽  
Castration Resistant

Abstract BACKGROUND Prostate cancer represents the most common non–skin cancer type in men. Unmet needs include understanding prognosis to determine when intervention is needed and what type, prediction to guide the choice of a systemic therapy, and response indicators to determine whether a treatment is working. Over the past decade, the “liquid biopsy,” characterized by the analysis of tumor cells and tumor cell products such as cell-free nucleic acids (DNA, microRNA) or extracellular vesicles circulating in the blood of cancer patients, has received considerable attention. CONTENT Among those biomarkers, circulating tumor cells (CTCs) have been most intensively analyzed in prostate cancer. Here we discuss recent studies on the enumeration and characterization of CTCs in peripheral blood and how this information can be used to develop biomarkers for each of these clinical contexts. We focus on clinical applications in men with metastatic castration-resistant prostate cancer, in whom CTCs are more often detected and at higher numbers, and clinical validation for different contexts of use is most mature. SUMMARY The overall goal of CTC-based liquid biopsy testing is to better inform medical decision-making so that patient outcomes are improved.

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