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Open AccessArticle

When Less Is More: Specific Capture and Analysis of Tumor Exosomes in Plasma Increases the Sensitivity of Liquid Biopsy for Comprehensive Detection of Multiple Androgen Receptor Phenotypes in Advanced Prostate Cancer Patients

1
CREA Laboratory (Centro di Ricerca Emato-Oncologica AIL), ASST Spedali Civili of Brescia, 25123 Brescia, Italy
2
Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
3
Exosomics S.p.A Siena, Strada del Petriccio e Belriguardo 35, 53100 Siena, Italy
4
Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
5
Radiation Oncology Department, University of Brescia, ASST Spedali Civili, 25123 Brescia, Italy
*
Authors to whom correspondence should be addressed.
Biomedicines 2020, 8(5), 131; https://doi.org/10.3390/biomedicines8050131
Received: 22 April 2020 / Revised: 14 May 2020 / Accepted: 19 May 2020 / Published: 22 May 2020
(This article belongs to the Special Issue Liquid Biopsies in Cancer Diagnosis, Monitoring and Prognosis)
We evaluated the advantages and the reliability of novel protocols for the enrichment of tumor extracellular vesicles (EVs), enabling a blood-based test for the noninvasive parallel profiling of multiple androgen receptor (AR) gene alterations. Three clinically relevant AR variants related to response/resistance to standard-of-care treatments (AR-V7 transcript, AR T878A point mutation and AR gene amplification) were evaluated by digital PCR in 15 samples from patients affected by Castration-Resistant Prostate Cancer (CRPC). Plasma was processed to obtain circulating RNA and DNA using protocols based on tumor EVs enrichment through immuno-affinity and peptide-affinity compared to generic extraction kits. Our results showed that immuno-affinity enrichment prior to RNA extraction clearly outperforms the generic isolation method in the detection of AR-V7, also allowing for a distinction between responder (R) and non-responder (NR) patients. The T878A mutation was detected, overall, in nine out of 15 samples and no approach alone was able to reveal mutations in all harboring samples, showing that the employed methods complement each other. AR amplification was detected in the majority of CRPC samples analysed using either cell-free DNA (cfDNA) or exosome isolation kits (80%). We demonstrated that selective isolation of a subset of circulating exosomes enriched for tumor origin, rather than analysis of total plasma exosomes, or total plasma nucleic acids, increases sensitivity and specificity for the detection of specific alterations. View Full-Text
Keywords: exosomes; extracellular vesicles; castration resistant prostate cancer; AR-V7; liquid biopsy exosomes; extracellular vesicles; castration resistant prostate cancer; AR-V7; liquid biopsy
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Foroni, C.; Zarovni, N.; Bianciardi, L.; Bernardi, S.; Triggiani, L.; Zocco, D.; Venturella, M.; Chiesi, A.; Valcamonico, F.; Berruti, A. When Less Is More: Specific Capture and Analysis of Tumor Exosomes in Plasma Increases the Sensitivity of Liquid Biopsy for Comprehensive Detection of Multiple Androgen Receptor Phenotypes in Advanced Prostate Cancer Patients. Biomedicines 2020, 8, 131.

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