Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients

Abstract Neuroendocrine prostate cancer (NEPC), a highly aggressive variant of castration-resistant prostate cancer (CRPC), often emerges upon treatment with androgen pathway inhibitors, via neuroendocrine differentiation. Currently, NEPC diagnosis is challenging as available markers are not suffici...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Divya Bhagirath, Michael Liston, Theresa Akoto, Byron Lui, Barbara A. Bensing, Ashok Sharma, Sharanjot Saini
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d5214699fc2a4b7883f1e1dd59762ab6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d5214699fc2a4b7883f1e1dd59762ab6
record_format	dspace
spelling	oai:doaj.org-article:d5214699fc2a4b7883f1e1dd59762ab62021-12-02T18:03:31ZNovel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients10.1038/s41598-021-87441-22045-2322https://doaj.org/article/d5214699fc2a4b7883f1e1dd59762ab62021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87441-2https://doaj.org/toc/2045-2322Abstract Neuroendocrine prostate cancer (NEPC), a highly aggressive variant of castration-resistant prostate cancer (CRPC), often emerges upon treatment with androgen pathway inhibitors, via neuroendocrine differentiation. Currently, NEPC diagnosis is challenging as available markers are not sufficiently specific. Our objective was to identify novel, extracellular vesicles (EV)-based biomarkers for diagnosing NEPC. Towards this, we performed small RNA next generation sequencing in serum EVs isolated from a cohort of CRPC patients with adenocarcinoma characteristics (CRPC-Adeno) vs CRPC-NE and identified significant dysregulation of 182 known and 4 novel miRNAs. We employed machine learning algorithms to develop an ‘EV-miRNA classifier’ that could robustly stratify ‘CRPC-NE’ from ‘CRPC-Adeno’. Examination of protein repertoire of exosomes from NEPC cellular models by mass spectrometry identified thrombospondin 1 (TSP1) as a specific biomarker. In view of our results, we propose that a miRNA panel and TSP1 can be used as novel, non-invasive tools to identify NEPC and guide treatment decisions. In conclusion, our study identifies for the first time, novel non-invasive exosomal/extracellular vesicle based biomarkers for detecting neuroendocrine differentiation in advanced castration resistant prostate cancer patients with important translational implications in clinical management of these patients that is currently extremely challenging.Divya BhagirathMichael ListonTheresa AkotoByron LuiBarbara A. BensingAshok SharmaSharanjot SainiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Divya Bhagirath Michael Liston Theresa Akoto Byron Lui Barbara A. Bensing Ashok Sharma Sharanjot Saini Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients
description	Abstract Neuroendocrine prostate cancer (NEPC), a highly aggressive variant of castration-resistant prostate cancer (CRPC), often emerges upon treatment with androgen pathway inhibitors, via neuroendocrine differentiation. Currently, NEPC diagnosis is challenging as available markers are not sufficiently specific. Our objective was to identify novel, extracellular vesicles (EV)-based biomarkers for diagnosing NEPC. Towards this, we performed small RNA next generation sequencing in serum EVs isolated from a cohort of CRPC patients with adenocarcinoma characteristics (CRPC-Adeno) vs CRPC-NE and identified significant dysregulation of 182 known and 4 novel miRNAs. We employed machine learning algorithms to develop an ‘EV-miRNA classifier’ that could robustly stratify ‘CRPC-NE’ from ‘CRPC-Adeno’. Examination of protein repertoire of exosomes from NEPC cellular models by mass spectrometry identified thrombospondin 1 (TSP1) as a specific biomarker. In view of our results, we propose that a miRNA panel and TSP1 can be used as novel, non-invasive tools to identify NEPC and guide treatment decisions. In conclusion, our study identifies for the first time, novel non-invasive exosomal/extracellular vesicle based biomarkers for detecting neuroendocrine differentiation in advanced castration resistant prostate cancer patients with important translational implications in clinical management of these patients that is currently extremely challenging.
format	article
author	Divya Bhagirath Michael Liston Theresa Akoto Byron Lui Barbara A. Bensing Ashok Sharma Sharanjot Saini
author_facet	Divya Bhagirath Michael Liston Theresa Akoto Byron Lui Barbara A. Bensing Ashok Sharma Sharanjot Saini
author_sort	Divya Bhagirath
title	Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients
title_short	Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients
title_full	Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients
title_fullStr	Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients
title_full_unstemmed	Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients
title_sort	novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d5214699fc2a4b7883f1e1dd59762ab6
work_keys_str_mv	AT divyabhagirath novelnoninvasivemarkersfordetectingtherapyinducedneuroendocrinedifferentiationincastrationresistantprostatecancerpatients AT michaelliston novelnoninvasivemarkersfordetectingtherapyinducedneuroendocrinedifferentiationincastrationresistantprostatecancerpatients AT theresaakoto novelnoninvasivemarkersfordetectingtherapyinducedneuroendocrinedifferentiationincastrationresistantprostatecancerpatients AT byronlui novelnoninvasivemarkersfordetectingtherapyinducedneuroendocrinedifferentiationincastrationresistantprostatecancerpatients AT barbaraabensing novelnoninvasivemarkersfordetectingtherapyinducedneuroendocrinedifferentiationincastrationresistantprostatecancerpatients AT ashoksharma novelnoninvasivemarkersfordetectingtherapyinducedneuroendocrinedifferentiationincastrationresistantprostatecancerpatients AT sharanjotsaini novelnoninvasivemarkersfordetectingtherapyinducedneuroendocrinedifferentiationincastrationresistantprostatecancerpatients
_version_	1718378715806695424

Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients

Ejemplares similares