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Transcriptome-Based Dissection of Intracranial Aneurysms Unveils an “Immuno-Thermal” Microenvironment and Defines a Pathological Feature-Derived Gene Signature for Risk Estimation

Immune inflammation plays an essential role in the formation and rupture of intracranial aneurysm (IA). However, the current limited knowledge of alterations in the immune microenvironment of IA has hampered the mastery of pathological mechanisms and technological advances, such as molecular diagnos...

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Autores principales: Lu, Taoyuan, Liu, Zaoqu, Guo, Dehua, Ma, Chi, Duan, Lin, He, Yanyan, Jia, Rufeng, Guo, Chunguang, Xing, Zhe, Liu, Yiying, Li, Tianxiao, He, Yingkun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194475/
https://www.ncbi.nlm.nih.gov/pubmed/35711443
http://dx.doi.org/10.3389/fimmu.2022.878195
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author Lu, Taoyuan
Liu, Zaoqu
Guo, Dehua
Ma, Chi
Duan, Lin
He, Yanyan
Jia, Rufeng
Guo, Chunguang
Xing, Zhe
Liu, Yiying
Li, Tianxiao
He, Yingkun
author_facet Lu, Taoyuan
Liu, Zaoqu
Guo, Dehua
Ma, Chi
Duan, Lin
He, Yanyan
Jia, Rufeng
Guo, Chunguang
Xing, Zhe
Liu, Yiying
Li, Tianxiao
He, Yingkun
author_sort Lu, Taoyuan
collection PubMed
description Immune inflammation plays an essential role in the formation and rupture of intracranial aneurysm (IA). However, the current limited knowledge of alterations in the immune microenvironment of IA has hampered the mastery of pathological mechanisms and technological advances, such as molecular diagnostic and coated stent-based molecular therapy. In this study, seven IA datasets were enrolled from the GEO database to decode the immune microenvironment and relevant biometric alterations. The ssGSEA algorithm was employed for immune infiltration assessment. IAs displayed abundant immune cell infiltration, activated immune-related pathways, and high expression of immune-related genes. Several immunosuppression cells and genes were also coordinately upregulated in IAs. Five immune-related hub genes, including CXCL10, IL6, IL10, STAT1, and VEGFA, were identified from the protein-protein interaction network and further detected at the protein level. CeRNA networks and latent drugs targeting the hub genes were predicted for targeted therapy reference. Two gene modules recognized via WCGNA were functionally associated with contractile smooth muscle loss and extracellular matrix metabolism, respectively. In blood datasets, a pathological feature-derived gene signature (PFDGS) for IA diagnosis and rupture risk prediction was established using machine learning. Patients with high PFDGS scores may possess adverse biological alterations and present with a high risk of morbidity or IA rupture, requiring more vigilance or prompt intervention. Overall, we systematically unveiled an “immuno-thermal” microenvironment characterized by co-enhanced immune activation and immunosuppression in IA, which provides a novel insight into molecular pathology. The PFDGS is a promising signature for optimizing risk surveillance and clinical decision-making in IA patients.
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spelling pubmed-91944752022-06-15 Transcriptome-Based Dissection of Intracranial Aneurysms Unveils an “Immuno-Thermal” Microenvironment and Defines a Pathological Feature-Derived Gene Signature for Risk Estimation Lu, Taoyuan Liu, Zaoqu Guo, Dehua Ma, Chi Duan, Lin He, Yanyan Jia, Rufeng Guo, Chunguang Xing, Zhe Liu, Yiying Li, Tianxiao He, Yingkun Front Immunol Immunology Immune inflammation plays an essential role in the formation and rupture of intracranial aneurysm (IA). However, the current limited knowledge of alterations in the immune microenvironment of IA has hampered the mastery of pathological mechanisms and technological advances, such as molecular diagnostic and coated stent-based molecular therapy. In this study, seven IA datasets were enrolled from the GEO database to decode the immune microenvironment and relevant biometric alterations. The ssGSEA algorithm was employed for immune infiltration assessment. IAs displayed abundant immune cell infiltration, activated immune-related pathways, and high expression of immune-related genes. Several immunosuppression cells and genes were also coordinately upregulated in IAs. Five immune-related hub genes, including CXCL10, IL6, IL10, STAT1, and VEGFA, were identified from the protein-protein interaction network and further detected at the protein level. CeRNA networks and latent drugs targeting the hub genes were predicted for targeted therapy reference. Two gene modules recognized via WCGNA were functionally associated with contractile smooth muscle loss and extracellular matrix metabolism, respectively. In blood datasets, a pathological feature-derived gene signature (PFDGS) for IA diagnosis and rupture risk prediction was established using machine learning. Patients with high PFDGS scores may possess adverse biological alterations and present with a high risk of morbidity or IA rupture, requiring more vigilance or prompt intervention. Overall, we systematically unveiled an “immuno-thermal” microenvironment characterized by co-enhanced immune activation and immunosuppression in IA, which provides a novel insight into molecular pathology. The PFDGS is a promising signature for optimizing risk surveillance and clinical decision-making in IA patients. Frontiers Media S.A. 2022-05-31 /pmc/articles/PMC9194475/ /pubmed/35711443 http://dx.doi.org/10.3389/fimmu.2022.878195 Text en Copyright © 2022 Lu, Liu, Guo, Ma, Duan, He, Jia, Guo, Xing, Liu, Li and He https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lu, Taoyuan
Liu, Zaoqu
Guo, Dehua
Ma, Chi
Duan, Lin
He, Yanyan
Jia, Rufeng
Guo, Chunguang
Xing, Zhe
Liu, Yiying
Li, Tianxiao
He, Yingkun
Transcriptome-Based Dissection of Intracranial Aneurysms Unveils an “Immuno-Thermal” Microenvironment and Defines a Pathological Feature-Derived Gene Signature for Risk Estimation
title Transcriptome-Based Dissection of Intracranial Aneurysms Unveils an “Immuno-Thermal” Microenvironment and Defines a Pathological Feature-Derived Gene Signature for Risk Estimation
title_full Transcriptome-Based Dissection of Intracranial Aneurysms Unveils an “Immuno-Thermal” Microenvironment and Defines a Pathological Feature-Derived Gene Signature for Risk Estimation
title_fullStr Transcriptome-Based Dissection of Intracranial Aneurysms Unveils an “Immuno-Thermal” Microenvironment and Defines a Pathological Feature-Derived Gene Signature for Risk Estimation
title_full_unstemmed Transcriptome-Based Dissection of Intracranial Aneurysms Unveils an “Immuno-Thermal” Microenvironment and Defines a Pathological Feature-Derived Gene Signature for Risk Estimation
title_short Transcriptome-Based Dissection of Intracranial Aneurysms Unveils an “Immuno-Thermal” Microenvironment and Defines a Pathological Feature-Derived Gene Signature for Risk Estimation
title_sort transcriptome-based dissection of intracranial aneurysms unveils an “immuno-thermal” microenvironment and defines a pathological feature-derived gene signature for risk estimation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194475/
https://www.ncbi.nlm.nih.gov/pubmed/35711443
http://dx.doi.org/10.3389/fimmu.2022.878195
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