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      A role of inflammaging in aortic aneurysm: new insights from bioinformatics analysis

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          Abstract

          Introduction

          Aortic aneurysms (AA) are prevalent worldwide with a notable absence of drug therapies. Thus, identifying potential drug targets is of utmost importance. AA often presents in the elderly, coupled with consistently raised serum inflammatory markers. Given that ageing and inflammation are pivotal processes linked to the evolution of AA, we have identified key genes involved in the inflammaging process of AA development through various bioinformatics methods, thereby providing potential molecular targets for further investigation.

          Methods

          The transcriptome data of AA was procured from the datasets GSE140947, GSE7084, and GSE47472, sourced from the NCBI GEO database, whilst gene data of ageing and inflammation were obtained from the GeneCards Database. To identify key genes, differentially expressed analysis using the “Limma” package and WGCNA were implemented. Protein-protein intersection (PPI) analysis and machine learning (ML) algorithms were employed for the screening of potential biomarkers, followed by an assessment of the diagnostic value. Following the acquisition of the hub inflammaging and AA-related differentially expressed genes (IADEGs), the TFs-mRNAs-miRNAs regulatory network was established. The CIBERSORT algorithm was utilized to investigate immune cell infiltration in AA. The correlation of hub IADEGs with infiltrating immunocytes was also evaluated. Lastly, wet laboratory experiments were carried out to confirm the expression of hub IADEGs.

          Results

          342 and 715 AA-related DEGs (ADEGs) recognized from GSE140947 and GSE7084 datasets were procured by intersecting the results of “Limma” and WGCNA analyses. After 83 IADEGs were obtained, PPI analysis and ML algorithms pinpointed 7 and 5 hub IADEGs candidates respectively, and 6 of them demonstrated a high diagnostic value. Immune cell infiltration outcomes unveiled immune dysregulation in AA. In the wet laboratory experiments, 3 hub IADEGs, including BLNK, HLA-DRA, and HLA-DQB1, finally exhibited an expression trend in line with the bioinformatics analysis result.

          Discussion

          Our research identified three genes - BLNK, HLA-DRA, and HLA-DQB1- that play a significant role in promoting the development of AA through inflammaging, providing novel insights into the future understanding and therapeutic intervention of AA.

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          Most cited references88

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          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

            Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
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              clusterProfiler: an R package for comparing biological themes among gene clusters.

              Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2140737Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2226606Role: Role: Role: Role: Role:
                Role: Role: Role: Role:
                Role: Role: Role: Role:
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                URI : https://loop.frontiersin.org/people/1880495Role: Role:
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                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                06 September 2023
                2023
                : 14
                : 1260688
                Affiliations
                [1] 1 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
                [2] 2 Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
                Author notes

                Edited by: Qiulun Lu, Nanjing Medical University, China

                Reviewed by: Kongyang Ma, Sun Yat-sen University, China; Wenjian Jiang, Capital Medical University, China

                †These authors have contributed equally to this work and share first authorship

                ‡These authors have contributed equally to this work and share last authorship

                Article
                10.3389/fimmu.2023.1260688
                10511768
                37744379
                226c2baa-72ea-45ef-aef6-3e47ab4e317b
                Copyright © 2023 Wang, Liu, Yang, Wang, Ye, Xia and Chen

                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.

                History
                : 18 July 2023
                : 23 August 2023
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 88, Pages: 16, Words: 6687
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 82170504, 81730015
                Funded by: Natural Science Foundation of Hubei Province , doi 10.13039/501100003819;
                Award ID: 2023AFB1042
                This study was funded by the Natural Science Foundation of Hubei Province (grant 2023AFB1042 to SC) and National Natural Science Foundation of China (grant 82170504 and 81730015 to JX).
                Categories
                Immunology
                Original Research
                Custom metadata
                Inflammation

                Immunology
                aortic aneurysms,inflammaging,ageing,inflammation,bioinformatics analysis
                Immunology
                aortic aneurysms, inflammaging, ageing, inflammation, bioinformatics analysis

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