Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection

Despite the diversity of liquid biopsy transcriptomic repertoire, numerous studies often exploit only a single RNA type signature for diagnostic biomarker potential. This frequently results in insufficient sensitivity and specificity necessary to reach diagnostic utility. Combinatorial biomarker app...

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Autores: D'Ambrosi, Silvia, Giannoukakos, Stavros|||0000-0001-8190-4199, Antunes-Ferreira, Mafalda|||0000-0001-6644-8930, Pedraz-Valdunciel, Carlos|||0000-0002-3163-2444, Bracht, Jillian|||0000-0001-9552-3960, Potie, Nicolas, Giménez-Capitán, Ana|||0000-0003-2575-1225, Hackenberg, Michael|||0000-0003-2248-3114, Fernandez Hilario, Alberto|||0000-0002-6480-8434, Molina Vila, Miguel Ángel|||0000-0001-8866-9881, Rosell, Rafael|||0000-0003-0817-3400, Würdinger, Thomas, Koppers-Lalic, Danijela|||0000-0002-1050-7521
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:280940
Acceso en línea:https://ddd.uab.cat/record/280940
https://dx.doi.org/urn:doi:10.3390/ijms24054881
Access Level:acceso abierto
Palabra clave:Biomarkers
Cancer diagnosis
Circular RNA
Liquid biopsy
Lung cancer
Messenger RNA
Platelets
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spelling Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer DetectionD'Ambrosi, SilviaGiannoukakos, Stavros|||0000-0001-8190-4199Antunes-Ferreira, Mafalda|||0000-0001-6644-8930Pedraz-Valdunciel, Carlos|||0000-0002-3163-2444Bracht, Jillian|||0000-0001-9552-3960Potie, NicolasGiménez-Capitán, Ana|||0000-0003-2575-1225Hackenberg, Michael|||0000-0003-2248-3114Fernandez Hilario, Alberto|||0000-0002-6480-8434Molina Vila, Miguel Ángel|||0000-0001-8866-9881Rosell, Rafael|||0000-0003-0817-3400Würdinger, ThomasKoppers-Lalic, Danijela|||0000-0002-1050-7521BiomarkersCancer diagnosisCircular RNALiquid biopsyLung cancerMessenger RNAPlateletsDespite the diversity of liquid biopsy transcriptomic repertoire, numerous studies often exploit only a single RNA type signature for diagnostic biomarker potential. This frequently results in insufficient sensitivity and specificity necessary to reach diagnostic utility. Combinatorial biomarker approaches may offer a more reliable diagnosis. Here, we investigated the synergistic contributions of circRNA and mRNA signatures derived from blood platelets as biomarkers for lung cancer detection. We developed a comprehensive bioinformatics pipeline permitting an analysis of platelet-circRNA and mRNA derived from non-cancer individuals and lung cancer patients. An optimal selected signature is then used to generate the predictive classification model using machine learning algorithm. Using an individual signature of 21 circRNA and 28 mRNA, the predictive models reached an area under the curve (AUC) of 0.88 and 0.81, respectively. Importantly, combinatorial analysis including both types of RNAs resulted in an 8-target signature (6 mRNA and 2 circRNA), enhancing the differentiation of lung cancer from controls (AUC of 0.92). Additionally, we identified five biomarkers potentially specific for early-stage detection of lung cancer. Our proof-of-concept study presents the first multi-analyte-based approach for the analysis of platelets-derived biomarkers, providing a potential combinatorial diagnostic signature for lung cancer detection.Universitat Autònoma de Barcelona 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/280940https://dx.doi.org/urn:doi:10.3390/ijms24054881reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2809402026-06-06T12:50:31Z
dc.title.none.fl_str_mv Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection
title Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection
spellingShingle Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection
D'Ambrosi, Silvia
Biomarkers
Cancer diagnosis
Circular RNA
Liquid biopsy
Lung cancer
Messenger RNA
Platelets
title_short Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection
title_full Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection
title_fullStr Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection
title_full_unstemmed Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection
title_sort Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection
dc.creator.none.fl_str_mv D'Ambrosi, Silvia
Giannoukakos, Stavros|||0000-0001-8190-4199
Antunes-Ferreira, Mafalda|||0000-0001-6644-8930
Pedraz-Valdunciel, Carlos|||0000-0002-3163-2444
Bracht, Jillian|||0000-0001-9552-3960
Potie, Nicolas
Giménez-Capitán, Ana|||0000-0003-2575-1225
Hackenberg, Michael|||0000-0003-2248-3114
Fernandez Hilario, Alberto|||0000-0002-6480-8434
Molina Vila, Miguel Ángel|||0000-0001-8866-9881
Rosell, Rafael|||0000-0003-0817-3400
Würdinger, Thomas
Koppers-Lalic, Danijela|||0000-0002-1050-7521
author D'Ambrosi, Silvia
author_facet D'Ambrosi, Silvia
Giannoukakos, Stavros|||0000-0001-8190-4199
Antunes-Ferreira, Mafalda|||0000-0001-6644-8930
Pedraz-Valdunciel, Carlos|||0000-0002-3163-2444
Bracht, Jillian|||0000-0001-9552-3960
Potie, Nicolas
Giménez-Capitán, Ana|||0000-0003-2575-1225
Hackenberg, Michael|||0000-0003-2248-3114
Fernandez Hilario, Alberto|||0000-0002-6480-8434
Molina Vila, Miguel Ángel|||0000-0001-8866-9881
Rosell, Rafael|||0000-0003-0817-3400
Würdinger, Thomas
Koppers-Lalic, Danijela|||0000-0002-1050-7521
author_role author
author2 Giannoukakos, Stavros|||0000-0001-8190-4199
Antunes-Ferreira, Mafalda|||0000-0001-6644-8930
Pedraz-Valdunciel, Carlos|||0000-0002-3163-2444
Bracht, Jillian|||0000-0001-9552-3960
Potie, Nicolas
Giménez-Capitán, Ana|||0000-0003-2575-1225
Hackenberg, Michael|||0000-0003-2248-3114
Fernandez Hilario, Alberto|||0000-0002-6480-8434
Molina Vila, Miguel Ángel|||0000-0001-8866-9881
Rosell, Rafael|||0000-0003-0817-3400
Würdinger, Thomas
Koppers-Lalic, Danijela|||0000-0002-1050-7521
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Biomarkers
Cancer diagnosis
Circular RNA
Liquid biopsy
Lung cancer
Messenger RNA
Platelets
topic Biomarkers
Cancer diagnosis
Circular RNA
Liquid biopsy
Lung cancer
Messenger RNA
Platelets
description Despite the diversity of liquid biopsy transcriptomic repertoire, numerous studies often exploit only a single RNA type signature for diagnostic biomarker potential. This frequently results in insufficient sensitivity and specificity necessary to reach diagnostic utility. Combinatorial biomarker approaches may offer a more reliable diagnosis. Here, we investigated the synergistic contributions of circRNA and mRNA signatures derived from blood platelets as biomarkers for lung cancer detection. We developed a comprehensive bioinformatics pipeline permitting an analysis of platelet-circRNA and mRNA derived from non-cancer individuals and lung cancer patients. An optimal selected signature is then used to generate the predictive classification model using machine learning algorithm. Using an individual signature of 21 circRNA and 28 mRNA, the predictive models reached an area under the curve (AUC) of 0.88 and 0.81, respectively. Importantly, combinatorial analysis including both types of RNAs resulted in an 8-target signature (6 mRNA and 2 circRNA), enhancing the differentiation of lung cancer from controls (AUC of 0.92). Additionally, we identified five biomarkers potentially specific for early-stage detection of lung cancer. Our proof-of-concept study presents the first multi-analyte-based approach for the analysis of platelets-derived biomarkers, providing a potential combinatorial diagnostic signature for lung cancer detection.
publishDate 2023
dc.date.none.fl_str_mv 2
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/280940
https://dx.doi.org/urn:doi:10.3390/ijms24054881
url https://ddd.uab.cat/record/280940
https://dx.doi.org/urn:doi:10.3390/ijms24054881
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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