Two Novel Ceramide-Like Molecules and miR-5100 Levels as Biomarkers Improve Prediction of Prostate Cancer in Gray-Zone PSA

Reliable liquid biopsy-based tools able to accurately discriminate prostate cancer (PCa) from benign prostatic hyperplasia (BPH), when PSA is within the “gray zone” (PSA 4–10), are still urgent. We analyzed plasma samples from a cohort of 102 consecutively recruited patients with PSA levels between...

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Autores principales:	Maurizia Mello-Grand, Antonino Bruno, Lidia Sacchetto, Simone Cristoni, Ilaria Gregnanin, Alessandro Dematteis, Andrea Zitella, Paolo Gontero, Caterina Peraldo-Neia, Riccardo Ricotta, Douglas M. Noonan, Adriana Albini, Giovanna Chiorino
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	SANIST-CIMS ceramide miR-5100 prostate cancer benign prostatic hyperplasia liquid biopsy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/62a2a94d6e1142f6afb3f836b01fc657
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spelling	oai:doaj.org-article:62a2a94d6e1142f6afb3f836b01fc6572021-11-19T07:51:26ZTwo Novel Ceramide-Like Molecules and miR-5100 Levels as Biomarkers Improve Prediction of Prostate Cancer in Gray-Zone PSA2234-943X10.3389/fonc.2021.769158https://doaj.org/article/62a2a94d6e1142f6afb3f836b01fc6572021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.769158/fullhttps://doaj.org/toc/2234-943XReliable liquid biopsy-based tools able to accurately discriminate prostate cancer (PCa) from benign prostatic hyperplasia (BPH), when PSA is within the “gray zone” (PSA 4–10), are still urgent. We analyzed plasma samples from a cohort of 102 consecutively recruited patients with PSA levels between 4 and 16 ng/ml, using the SANIST-Cloud Ion Mobility Metabolomic Mass Spectrometry platform, combined with the analysis of a panel of circulating microRNAs (miR). By coupling CIMS ion mobility technology with SANIST, we were able to reveal three new structures among the most differentially expressed metabolites in PCa vs. BPH. In particular, two were classified as polyunsaturated ceramide ester-like and one as polysaturated glycerol ester-like. Penalized logistic regression was applied to build a model to predict PCa, using six circulating miR, seven circulating metabolites, and demographic/clinical variables, as covariates. Four circulating metabolites, miR-5100, and age were selected by the model, and the corresponding prediction score gave an AUC of 0.76 (C.I. = 0.66–0.85). At a specified cut-off, no high-risk tumor was misclassified, and 22 out of 53 BPH were correctly identified, reducing by 40% the false positives of PSA. We developed and applied a novel, minimally invasive, liquid biopsy-based powerful tool to characterize novel metabolites and identified new potential non-invasive biomarkers to better predict PCa, when PSA is uninformative as a tool for precision medicine in genitourinary cancers.Maurizia Mello-GrandAntonino BrunoLidia SacchettoSimone CristoniIlaria GregnaninAlessandro DematteisAndrea ZitellaPaolo GonteroCaterina Peraldo-NeiaRiccardo RicottaDouglas M. NoonanDouglas M. NoonanAdriana AlbiniGiovanna ChiorinoFrontiers Media S.A.articleSANIST-CIMSceramidemiR-5100prostate cancerbenign prostatic hyperplasialiquid biopsyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SANIST-CIMS ceramide miR-5100 prostate cancer benign prostatic hyperplasia liquid biopsy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	SANIST-CIMS ceramide miR-5100 prostate cancer benign prostatic hyperplasia liquid biopsy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Maurizia Mello-Grand Antonino Bruno Lidia Sacchetto Simone Cristoni Ilaria Gregnanin Alessandro Dematteis Andrea Zitella Paolo Gontero Caterina Peraldo-Neia Riccardo Ricotta Douglas M. Noonan Douglas M. Noonan Adriana Albini Giovanna Chiorino Two Novel Ceramide-Like Molecules and miR-5100 Levels as Biomarkers Improve Prediction of Prostate Cancer in Gray-Zone PSA
description	Reliable liquid biopsy-based tools able to accurately discriminate prostate cancer (PCa) from benign prostatic hyperplasia (BPH), when PSA is within the “gray zone” (PSA 4–10), are still urgent. We analyzed plasma samples from a cohort of 102 consecutively recruited patients with PSA levels between 4 and 16 ng/ml, using the SANIST-Cloud Ion Mobility Metabolomic Mass Spectrometry platform, combined with the analysis of a panel of circulating microRNAs (miR). By coupling CIMS ion mobility technology with SANIST, we were able to reveal three new structures among the most differentially expressed metabolites in PCa vs. BPH. In particular, two were classified as polyunsaturated ceramide ester-like and one as polysaturated glycerol ester-like. Penalized logistic regression was applied to build a model to predict PCa, using six circulating miR, seven circulating metabolites, and demographic/clinical variables, as covariates. Four circulating metabolites, miR-5100, and age were selected by the model, and the corresponding prediction score gave an AUC of 0.76 (C.I. = 0.66–0.85). At a specified cut-off, no high-risk tumor was misclassified, and 22 out of 53 BPH were correctly identified, reducing by 40% the false positives of PSA. We developed and applied a novel, minimally invasive, liquid biopsy-based powerful tool to characterize novel metabolites and identified new potential non-invasive biomarkers to better predict PCa, when PSA is uninformative as a tool for precision medicine in genitourinary cancers.
format	article
author	Maurizia Mello-Grand Antonino Bruno Lidia Sacchetto Simone Cristoni Ilaria Gregnanin Alessandro Dematteis Andrea Zitella Paolo Gontero Caterina Peraldo-Neia Riccardo Ricotta Douglas M. Noonan Douglas M. Noonan Adriana Albini Giovanna Chiorino
author_facet	Maurizia Mello-Grand Antonino Bruno Lidia Sacchetto Simone Cristoni Ilaria Gregnanin Alessandro Dematteis Andrea Zitella Paolo Gontero Caterina Peraldo-Neia Riccardo Ricotta Douglas M. Noonan Douglas M. Noonan Adriana Albini Giovanna Chiorino
author_sort	Maurizia Mello-Grand
title	Two Novel Ceramide-Like Molecules and miR-5100 Levels as Biomarkers Improve Prediction of Prostate Cancer in Gray-Zone PSA
title_short	Two Novel Ceramide-Like Molecules and miR-5100 Levels as Biomarkers Improve Prediction of Prostate Cancer in Gray-Zone PSA
title_full	Two Novel Ceramide-Like Molecules and miR-5100 Levels as Biomarkers Improve Prediction of Prostate Cancer in Gray-Zone PSA
title_fullStr	Two Novel Ceramide-Like Molecules and miR-5100 Levels as Biomarkers Improve Prediction of Prostate Cancer in Gray-Zone PSA
title_full_unstemmed	Two Novel Ceramide-Like Molecules and miR-5100 Levels as Biomarkers Improve Prediction of Prostate Cancer in Gray-Zone PSA
title_sort	two novel ceramide-like molecules and mir-5100 levels as biomarkers improve prediction of prostate cancer in gray-zone psa
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/62a2a94d6e1142f6afb3f836b01fc657
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Two Novel Ceramide-Like Molecules and miR-5100 Levels as Biomarkers Improve Prediction of Prostate Cancer in Gray-Zone PSA

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