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

D’Ambrosi, Silvia; Giannoukakos, Stavros; Antunes-Ferreira, Mafalda; Pedraz-Valdunciel, Carlos; Bracht, Jillian W. P.; Potie, Nicolas; Gimenez-Capitan, Ana; Hackenberg, Michael; Fernandez Hilario, Alberto; Molina-Vila, Miguel A.; Rosell, Rafael; Würdinger, Thomas; Koppers-Lalic, Danijela

doi:10.3390/ijms24054881

Open AccessArticle

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

by

Silvia D’Ambrosi

¹,

Stavros Giannoukakos

^2,3,†

,

Mafalda Antunes-Ferreira

^1,†

,

Carlos Pedraz-Valdunciel

^4,5

,

Jillian W. P. Bracht

⁶

,

Nicolas Potie

^2,3,

Ana Gimenez-Capitan

⁶

,

Michael Hackenberg

^2,3

,

Alberto Fernandez Hilario

⁷

,

Miguel A. Molina-Vila

⁶

,

Rafael Rosell

⁵,

Thomas Würdinger

^1,8,* and

Danijela Koppers-Lalic

^9,*

¹

Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands

²

Department of Genetics, Faculty of Science, University of Granada, 18071 Granada, Spain

³

Bioinformatics Laboratory, Biomedical Research Centre (CIBM), PTS, 18100 Granada, Spain

⁴

Department of Biochemistry, Molecular Biology and Biomedicine, Universitat Autónoma de Barcelona (UAB), 08193 Cerdanyola, Spain

⁵

Germans Trias i Pujol Health Sciences Institute and Hospital (IGTP), 08916 Barcelona, Spain

⁶

Pangaea Oncology—Laboratory of Oncology, Quirón Dexeus University Hospital, Sabino Arana 5-19, 08028 Barcelona, Spain

⁷

Andalusian Research Institute in Data Science and Computational Intelligence, University of Granada, 18071 Granada, Spain

⁸

Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands

⁹

Mathematical Institute, Leiden University, 2333 CA Leiden, The Netherlands

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2023, 24(5), 4881; https://doi.org/10.3390/ijms24054881

Submission received: 11 January 2023 / Revised: 21 February 2023 / Accepted: 21 February 2023 / Published: 2 March 2023

(This article belongs to the Special Issue New Diagnostic Tools and Biomarkers in Oncological Diseases)

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Abstract

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.

Keywords: liquid biopsy; biomarkers; circular RNA; messenger RNA; platelets; lung cancer; cancer diagnosis

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MDPI and ACS Style

D’Ambrosi, S.; Giannoukakos, S.; Antunes-Ferreira, M.; Pedraz-Valdunciel, C.; Bracht, J.W.P.; Potie, N.; Gimenez-Capitan, A.; Hackenberg, M.; Fernandez Hilario, A.; Molina-Vila, M.A.; et al. Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection. Int. J. Mol. Sci. 2023, 24, 4881. https://doi.org/10.3390/ijms24054881

AMA Style

D’Ambrosi S, Giannoukakos S, Antunes-Ferreira M, Pedraz-Valdunciel C, Bracht JWP, Potie N, Gimenez-Capitan A, Hackenberg M, Fernandez Hilario A, Molina-Vila MA, et al. Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection. International Journal of Molecular Sciences. 2023; 24(5):4881. https://doi.org/10.3390/ijms24054881

Chicago/Turabian Style

D’Ambrosi, Silvia, Stavros Giannoukakos, Mafalda Antunes-Ferreira, Carlos Pedraz-Valdunciel, Jillian W. P. Bracht, Nicolas Potie, Ana Gimenez-Capitan, Michael Hackenberg, Alberto Fernandez Hilario, Miguel A. Molina-Vila, and et al. 2023. "Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection" International Journal of Molecular Sciences 24, no. 5: 4881. https://doi.org/10.3390/ijms24054881

APA Style

D’Ambrosi, S., Giannoukakos, S., Antunes-Ferreira, M., Pedraz-Valdunciel, C., Bracht, J. W. P., Potie, N., Gimenez-Capitan, A., Hackenberg, M., Fernandez Hilario, A., Molina-Vila, M. A., Rosell, R., Würdinger, T., & Koppers-Lalic, D. (2023). Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection. International Journal of Molecular Sciences, 24(5), 4881. https://doi.org/10.3390/ijms24054881

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

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