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The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer

SIMPLE SUMMARY: Interaction between blood platelets and cancer cells play an important role in various steps of cancer development and progression. These interactions lead to changes in the platelets’ RNA content, resulting in tumor-mediated “education” of platelets. Tumor-educated platelets (TEPs)...

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Autores principales: D’Ambrosi, Silvia, Visser, Allerdien, Antunes-Ferreira, Mafalda, Poutsma, Ankie, Giannoukakos, Stavros, Sol, Nik, Sabrkhany, Siamack, Bahce, Idris, Kuijpers, Marijke J. E., Oude Egbrink, Mirjam G. A., Griffioen, Arjan W., Best, Myron G., Koppers-Lalic, Danijela, Oudejans, Cees, Würdinger, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468408/
https://www.ncbi.nlm.nih.gov/pubmed/34572871
http://dx.doi.org/10.3390/cancers13184644
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author D’Ambrosi, Silvia
Visser, Allerdien
Antunes-Ferreira, Mafalda
Poutsma, Ankie
Giannoukakos, Stavros
Sol, Nik
Sabrkhany, Siamack
Bahce, Idris
Kuijpers, Marijke J. E.
Oude Egbrink, Mirjam G. A.
Griffioen, Arjan W.
Best, Myron G.
Koppers-Lalic, Danijela
Oudejans, Cees
Würdinger, Thomas
author_facet D’Ambrosi, Silvia
Visser, Allerdien
Antunes-Ferreira, Mafalda
Poutsma, Ankie
Giannoukakos, Stavros
Sol, Nik
Sabrkhany, Siamack
Bahce, Idris
Kuijpers, Marijke J. E.
Oude Egbrink, Mirjam G. A.
Griffioen, Arjan W.
Best, Myron G.
Koppers-Lalic, Danijela
Oudejans, Cees
Würdinger, Thomas
author_sort D’Ambrosi, Silvia
collection PubMed
description SIMPLE SUMMARY: Interaction between blood platelets and cancer cells play an important role in various steps of cancer development and progression. These interactions lead to changes in the platelets’ RNA content, resulting in tumor-mediated “education” of platelets. Tumor-educated platelets (TEPs) can be used as a non-invasive biomarker source for cancer detection and progression monitoring. Our lab has previously identified that spliced mRNA TEP signatures provide specific information on the presence, location, and molecular features of cancers. Next to mRNA, other RNA types are present in platelets, and their repertoire can potentially be subjected to cancer-mediated alterations. Despite the evidence that circRNA could be a promising cancer biomarker, they have not yet been analyzed in blood platelets of cancer patients. In this proof-of-concept study, we aim to evaluate whether platelets’ circRNA signature could be used as a biomarker for cancer detection and progression. ABSTRACT: Tumor-educated Platelets (TEPs) have emerged as rich biosources of cancer-related RNA profiles in liquid biopsies applicable for cancer detection. Although human blood platelets have been found to be enriched in circular RNA (circRNA), no studies have investigated the potential of circRNA as platelet-derived biomarkers for cancer. In this proof-of-concept study, we examine whether the circRNA signature of blood platelets can be used as a liquid biopsy biomarker for the detection of non-small cell lung cancer (NSCLC). We analyzed the total RNA, extracted from the platelet samples collected from NSCLC patients and asymptomatic individuals, using RNA sequencing (RNA-Seq). Identification and quantification of known and novel circRNAs were performed using the accurate CircRNA finder suite (ACFS), followed by the differential transcript expression analysis using a modified version of our thromboSeq software. Out of 4732 detected circRNAs, we identified 411 circRNAs that are significantly (p-value < 0.05) differentially expressed between asymptomatic individuals and NSCLC patients. Using the false discovery rate (FDR) of 0.05 as cutoff, we selected the nuclear receptor-interacting protein 1 (NRIP1) circRNA (circNRIP1) as a potential biomarker candidate for further validation by reverse transcription–quantitative PCR (RT-qPCR). This analysis was performed on an independent cohort of platelet samples. The RT-qPCR results confirmed the RNA-Seq data analysis, with significant downregulation of circNRIP1 in platelets derived from NSCLC patients. Our findings suggest that circRNAs found in blood platelets may hold diagnostic biomarkers potential for the detection of NSCLC using liquid biopsies.
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spelling pubmed-84684082021-09-27 The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer D’Ambrosi, Silvia Visser, Allerdien Antunes-Ferreira, Mafalda Poutsma, Ankie Giannoukakos, Stavros Sol, Nik Sabrkhany, Siamack Bahce, Idris Kuijpers, Marijke J. E. Oude Egbrink, Mirjam G. A. Griffioen, Arjan W. Best, Myron G. Koppers-Lalic, Danijela Oudejans, Cees Würdinger, Thomas Cancers (Basel) Article SIMPLE SUMMARY: Interaction between blood platelets and cancer cells play an important role in various steps of cancer development and progression. These interactions lead to changes in the platelets’ RNA content, resulting in tumor-mediated “education” of platelets. Tumor-educated platelets (TEPs) can be used as a non-invasive biomarker source for cancer detection and progression monitoring. Our lab has previously identified that spliced mRNA TEP signatures provide specific information on the presence, location, and molecular features of cancers. Next to mRNA, other RNA types are present in platelets, and their repertoire can potentially be subjected to cancer-mediated alterations. Despite the evidence that circRNA could be a promising cancer biomarker, they have not yet been analyzed in blood platelets of cancer patients. In this proof-of-concept study, we aim to evaluate whether platelets’ circRNA signature could be used as a biomarker for cancer detection and progression. ABSTRACT: Tumor-educated Platelets (TEPs) have emerged as rich biosources of cancer-related RNA profiles in liquid biopsies applicable for cancer detection. Although human blood platelets have been found to be enriched in circular RNA (circRNA), no studies have investigated the potential of circRNA as platelet-derived biomarkers for cancer. In this proof-of-concept study, we examine whether the circRNA signature of blood platelets can be used as a liquid biopsy biomarker for the detection of non-small cell lung cancer (NSCLC). We analyzed the total RNA, extracted from the platelet samples collected from NSCLC patients and asymptomatic individuals, using RNA sequencing (RNA-Seq). Identification and quantification of known and novel circRNAs were performed using the accurate CircRNA finder suite (ACFS), followed by the differential transcript expression analysis using a modified version of our thromboSeq software. Out of 4732 detected circRNAs, we identified 411 circRNAs that are significantly (p-value < 0.05) differentially expressed between asymptomatic individuals and NSCLC patients. Using the false discovery rate (FDR) of 0.05 as cutoff, we selected the nuclear receptor-interacting protein 1 (NRIP1) circRNA (circNRIP1) as a potential biomarker candidate for further validation by reverse transcription–quantitative PCR (RT-qPCR). This analysis was performed on an independent cohort of platelet samples. The RT-qPCR results confirmed the RNA-Seq data analysis, with significant downregulation of circNRIP1 in platelets derived from NSCLC patients. Our findings suggest that circRNAs found in blood platelets may hold diagnostic biomarkers potential for the detection of NSCLC using liquid biopsies. MDPI 2021-09-16 /pmc/articles/PMC8468408/ /pubmed/34572871 http://dx.doi.org/10.3390/cancers13184644 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
D’Ambrosi, Silvia
Visser, Allerdien
Antunes-Ferreira, Mafalda
Poutsma, Ankie
Giannoukakos, Stavros
Sol, Nik
Sabrkhany, Siamack
Bahce, Idris
Kuijpers, Marijke J. E.
Oude Egbrink, Mirjam G. A.
Griffioen, Arjan W.
Best, Myron G.
Koppers-Lalic, Danijela
Oudejans, Cees
Würdinger, Thomas
The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer
title The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer
title_full The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer
title_fullStr The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer
title_full_unstemmed The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer
title_short The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer
title_sort analysis of platelet-derived circrna repertoire as potential diagnostic biomarker for non-small cell lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468408/
https://www.ncbi.nlm.nih.gov/pubmed/34572871
http://dx.doi.org/10.3390/cancers13184644
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