Next Article in Journal
Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity
Next Article in Special Issue
Anti-Cancer Auto-Antibodies: Roles, Applications and Open Issues
Previous Article in Journal
Preclinical and Clinical Status of PSMA-Targeted Alpha Therapy for Metastatic Castration-Resistant Prostate Cancer
Previous Article in Special Issue
Interferon Regulatory Factor 9 Promotes Lung Cancer Progression via Regulation of Versican
Article

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

1
Analysis of Circulating Tumor Cells Laboratory, Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece
2
Oncology Unit, 2nd Department of Surgery, Aretaieio Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece
*
Author to whom correspondence should be addressed.
Academic Editor: Theodoros Rampias
Cancers 2021, 13(4), 780; https://doi.org/10.3390/cancers13040780
Received: 5 January 2021 / Revised: 2 February 2021 / Accepted: 10 February 2021 / Published: 13 February 2021
(This article belongs to the Special Issue Tumor Evolution: Progression, Metastasis and Therapeutic Response)
“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. Our results revealed for the first time a significantly higher positivity of all markers in EpCAM-positive CTCs compared to plasma-derived exosomes. We report that in EpCAM-positive CTCs, CK-19, PSMA, TWIST1 expression and GSTP1 methylation are significantly correlated with worse overall survival (OS), while in exosomes, CK-8 expression and GSTP1 and RASSF1A methylation status were significantly correlated with a lower OS. We also enumerated CTC and tumor-derived extracellular vesicles (tdEVs) using CellSearch (CS) and found a correlation between the CTC and tumor-derived extracellular vesicles (tdEVs) enumeration values.
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. View Full-Text
Keywords: prostate cancer; liquid biopsy; CTCs; extracellular vesicles; exosomes; DNA methylation; gene expression; RT-qPCR; MSP prostate cancer; liquid biopsy; CTCs; extracellular vesicles; exosomes; DNA methylation; gene expression; RT-qPCR; MSP
Show Figures

Figure 1

MDPI and ACS Style

Zavridou, M.; Strati, A.; Bournakis, E.; Smilkou, S.; Tserpeli, V.; Lianidou, E. 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, 13, 780. https://doi.org/10.3390/cancers13040780

AMA Style

Zavridou M, Strati A, Bournakis E, Smilkou S, Tserpeli V, Lianidou E. 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; 13(4):780. https://doi.org/10.3390/cancers13040780

Chicago/Turabian Style

Zavridou, Martha, Areti Strati, Evangelos Bournakis, Stavroula Smilkou, Victoria Tserpeli, and Evi Lianidou. 2021. "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 13, no. 4: 780. https://doi.org/10.3390/cancers13040780

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop