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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Detalles Bibliográficos
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
Descripción
Sumario: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.