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Identification of Circulating Gene Expression Signatures of Intracranial Aneurysm in Peripheral Blood Mononuclear Cells

Peripheral blood mononuclear cells (PBMCs) play an important role in the inflammation that accompanies intracranial aneurysm (IA) pathophysiology. We hypothesized that PBMCs have different transcriptional profiles in patients harboring IAs as compared to IA-free controls, which could be the basis fo...

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Autores principales: Tutino, Vincent M., Zebraski, Haley R., Rajabzadeh-Oghaz, Hamidreza, Waqas, Muhammad, Jarvis, James N., Bach, Konrad, Mokin, Maxim, Snyder, Kenneth V., Siddiqui, Adnan H., Poppenberg, Kerry E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232768/
https://www.ncbi.nlm.nih.gov/pubmed/34203780
http://dx.doi.org/10.3390/diagnostics11061092
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author Tutino, Vincent M.
Zebraski, Haley R.
Rajabzadeh-Oghaz, Hamidreza
Waqas, Muhammad
Jarvis, James N.
Bach, Konrad
Mokin, Maxim
Snyder, Kenneth V.
Siddiqui, Adnan H.
Poppenberg, Kerry E.
author_facet Tutino, Vincent M.
Zebraski, Haley R.
Rajabzadeh-Oghaz, Hamidreza
Waqas, Muhammad
Jarvis, James N.
Bach, Konrad
Mokin, Maxim
Snyder, Kenneth V.
Siddiqui, Adnan H.
Poppenberg, Kerry E.
author_sort Tutino, Vincent M.
collection PubMed
description Peripheral blood mononuclear cells (PBMCs) play an important role in the inflammation that accompanies intracranial aneurysm (IA) pathophysiology. We hypothesized that PBMCs have different transcriptional profiles in patients harboring IAs as compared to IA-free controls, which could be the basis for potential blood-based biomarkers for the disease. To test this, we isolated PBMC RNA from whole blood of 52 subjects (24 with IA, 28 without) and performed next-generation RNA sequencing to obtain their transcriptomes. In a randomly assigned discovery cohort of n = 39 patients, we performed differential expression analysis to define an IA-associated signature of 54 genes (q < 0.05 and an absolute fold-change ≥ 1.3). In the withheld validation dataset, these genes could delineate patients with IAs from controls, as the majority of them still had the same direction of expression difference. Bioinformatics analyses by gene ontology enrichment analysis and Ingenuity Pathway Analysis (IPA) demonstrated enrichment of structural regulation processes, intracellular signaling function, regulation of ion transport, and cell adhesion. IPA analysis showed that these processes were likely coordinated through NF-kB, cytokine signaling, growth factors, and TNF activity. Correlation analysis with aneurysm size and risk assessment metrics showed that 4/54 genes were associated with rupture risk. These findings highlight the potential to develop predictive biomarkers from PBMCs to identify patients harboring IAs.
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spelling pubmed-82327682021-06-26 Identification of Circulating Gene Expression Signatures of Intracranial Aneurysm in Peripheral Blood Mononuclear Cells Tutino, Vincent M. Zebraski, Haley R. Rajabzadeh-Oghaz, Hamidreza Waqas, Muhammad Jarvis, James N. Bach, Konrad Mokin, Maxim Snyder, Kenneth V. Siddiqui, Adnan H. Poppenberg, Kerry E. Diagnostics (Basel) Article Peripheral blood mononuclear cells (PBMCs) play an important role in the inflammation that accompanies intracranial aneurysm (IA) pathophysiology. We hypothesized that PBMCs have different transcriptional profiles in patients harboring IAs as compared to IA-free controls, which could be the basis for potential blood-based biomarkers for the disease. To test this, we isolated PBMC RNA from whole blood of 52 subjects (24 with IA, 28 without) and performed next-generation RNA sequencing to obtain their transcriptomes. In a randomly assigned discovery cohort of n = 39 patients, we performed differential expression analysis to define an IA-associated signature of 54 genes (q < 0.05 and an absolute fold-change ≥ 1.3). In the withheld validation dataset, these genes could delineate patients with IAs from controls, as the majority of them still had the same direction of expression difference. Bioinformatics analyses by gene ontology enrichment analysis and Ingenuity Pathway Analysis (IPA) demonstrated enrichment of structural regulation processes, intracellular signaling function, regulation of ion transport, and cell adhesion. IPA analysis showed that these processes were likely coordinated through NF-kB, cytokine signaling, growth factors, and TNF activity. Correlation analysis with aneurysm size and risk assessment metrics showed that 4/54 genes were associated with rupture risk. These findings highlight the potential to develop predictive biomarkers from PBMCs to identify patients harboring IAs. MDPI 2021-06-15 /pmc/articles/PMC8232768/ /pubmed/34203780 http://dx.doi.org/10.3390/diagnostics11061092 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
Tutino, Vincent M.
Zebraski, Haley R.
Rajabzadeh-Oghaz, Hamidreza
Waqas, Muhammad
Jarvis, James N.
Bach, Konrad
Mokin, Maxim
Snyder, Kenneth V.
Siddiqui, Adnan H.
Poppenberg, Kerry E.
Identification of Circulating Gene Expression Signatures of Intracranial Aneurysm in Peripheral Blood Mononuclear Cells
title Identification of Circulating Gene Expression Signatures of Intracranial Aneurysm in Peripheral Blood Mononuclear Cells
title_full Identification of Circulating Gene Expression Signatures of Intracranial Aneurysm in Peripheral Blood Mononuclear Cells
title_fullStr Identification of Circulating Gene Expression Signatures of Intracranial Aneurysm in Peripheral Blood Mononuclear Cells
title_full_unstemmed Identification of Circulating Gene Expression Signatures of Intracranial Aneurysm in Peripheral Blood Mononuclear Cells
title_short Identification of Circulating Gene Expression Signatures of Intracranial Aneurysm in Peripheral Blood Mononuclear Cells
title_sort identification of circulating gene expression signatures of intracranial aneurysm in peripheral blood mononuclear cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232768/
https://www.ncbi.nlm.nih.gov/pubmed/34203780
http://dx.doi.org/10.3390/diagnostics11061092
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