Bioinformatics analysis of potential common pathogenic mechanism for carotid atherosclerosis and Parkinson's disease

被引:1
作者
Wang, Quan [1 ]
Xue, Qun [1 ]
机构
[1] Soochow Univ, Affiliated Hosp 1, Dept Neurol, Suzhou, Peoples R China
来源
FRONTIERS IN AGING NEUROSCIENCE | 2023年 / 15卷
关键词
atherosclerosis; Parkinson's disease; bioinformatics analysis; hub genes; immune cells infiltration; NEUROCIRCULATORY ABNORMALITIES; P2X7; RECEPTOR; DEFICIENCY; PERTUSSIS; C1Q; NEURODEGENERATION; IMMUNOGLOBULINS; ASSOCIATION; DYSFUNCTION; IMMUNOLOGY;
D O I
10.3389/fnagi.2023.1202952
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Background Cerebrovascular disease (CVD) related to atherosclerosis and Parkinson's disease (PD) are two prevalent neurological disorders. They share common risk factors and frequently occur together. The aim of this study is to investigate the association between atherosclerosis and PD using genetic databases to gain a comprehensive understanding of underlying biological mechanisms.Methods The gene expression profiles of atherosclerosis (GSE28829 and GSE100927) and PD (GSE7621 and GSE49036) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) for these two disorders, we constructed protein-protein interaction (PPI) networks and functional modules, and further identified hub genes using Least Absolute Shrinkage and Selection Operator (LASSO) regression. The diagnostic effectiveness of these hub genes was evaluated using Receiver Operator Characteristic Curve (ROC) analysis. Furthermore, we used single sample gene set enrichment analysis (ssGSEA) to analyze immune cell infiltration and explored the association of the identified hub genes with infiltrating immune cells through Spearman's rank correlation analysis in R software.Results A total of 50 shared DEGs, with 36 up-regulated and 14 down-regulated genes, were identified through the intersection of DEGs of atherosclerosis and PD. Using LASSO regression, we identified six hub genes, namely C1QB, CD53, LY96, P2RX7, C3, and TNFSF13B, in the lambda.min model, and CD14, C1QB, CD53, P2RX7, C3, and TNFSF13B in the lambda.1se model. ROC analysis confirmed that both models had good diagnostic efficiency for atherosclerosis datasets GSE28829 (lambda.min AUC = 0.99, lambda.1se AUC = 0.986) and GSE100927 (lambda.min AUC = 0.922, lambda.1se AUC = 0.933), as well as for PD datasets GSE7621 (lambda.min AUC = 0.924, lambda.1se AUC = 0.944) and GSE49036 (lambda.min AUC = 0.894, lambda.1se AUC = 0.881). Furthermore, we found that activated B cells, effector memory CD8 + T cells, and macrophages were the shared correlated types of immune cells in both atherosclerosis and PD.Conclusion This study provided new sights into shared molecular mechanisms between these two disorders. These common hub genes and infiltrating immune cells offer promising clues for further experimental studies to explore the common pathogenesis of these disorders.
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页数:16
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  • [1] Cardiovascular and cerebrovascular risk markers in Parkinson's disease: Results from a case-control study
    Alves, Mariana
    Lobo, Patricia Pita
    Kauppila, Linda Azevedo
    Rebordao, Leonor
    Cruz, M. Manuela
    Soares, Fatima
    Cruz, Joao
    Tornada, Ana
    Caldeira, Daniel
    Reimao, Sofia
    Oliveira, Victor
    Ferro, Jose M.
    Ferreira, Joaquim J.
    [J]. EUROPEAN JOURNAL OF NEUROLOGY, 2021, 28 (08) : 2669 - 2679
  • [2] C-Reactive Protein in Atherothrombosis and Angiogenesis
    Badimon, Lina
    Pena, Esther
    Arderiu, Gemma
    Padro, Teresa
    Slevin, Mark
    Vilahur, Gemma
    Chiva-Blanch, Gemma
    [J]. FRONTIERS IN IMMUNOLOGY, 2018, 9
  • [3] Complement C1q reduces early atherosclerosis in low-density lipoprotein receptor-deficient mice
    Bhatia, Vinay K.
    Yun, Sheng
    Leung, Viola
    Grimsditch, David C.
    Benson, G. Martin
    Botto, Marina B.
    Boyle, Joseph J.
    Haskard, Dorian O.
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2007, 170 (01) : 416 - 426
  • [4] The genetic architecture of Parkinson's disease
    Blauwendraat, Cornelis
    Nalls, Mike A.
    Singleton, Andrew B.
    [J]. LANCET NEUROLOGY, 2020, 19 (02) : 170 - 178
  • [5] Parkinson's disease
    Bloem, Bastiaan R.
    Okun, Michael S.
    Klein, Christine
    [J]. LANCET, 2021, 397 (10291) : 2284 - 2303
  • [6] Influence of C3 deficiency on atherosclerosis
    Buono, C
    Come, CE
    Witztum, JL
    Maguire, GF
    Connelly, PW
    Carroll, M
    Lichtman, AH
    [J]. CIRCULATION, 2002, 105 (25) : 3025 - 3031
  • [7] The P2X7 receptor antagonist Brilliant Blue G attenuates contralateral rotations in a rat model of Parkinsonism through a combined control of synaptotoxicity, neurotoxicity and gliosis
    Carmo, Marta R. S.
    Menezes, Ana Paula F.
    Nunes, Ana Carla L.
    Pliassova, Anna
    Rolo, Anabela P.
    Palmeira, Carlos M.
    Cunha, Rodrigo A.
    Canas, Paula M.
    Andrade, Geanne M.
    [J]. NEUROPHARMACOLOGY, 2014, 81 : 142 - 152
  • [8] Identification and characterization of splice variants of the human P2X7 ATP channel
    Cheewatrakoolpong, B
    Gilchrest, H
    Anthes, JC
    Greenfeder, S
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 332 (01) : 17 - 27
  • [9] Increased P2X7 Receptor Binding Is Associated With Neuroinflammation in Acute but Not Chronic Rodent Models for Parkinson's Disease
    Crabbe, Melissa
    Van der Perren, Anke
    Bollaerts, Ilse
    Kounelis, Savannah
    Baekelandt, Veerle
    Bormans, Guy
    Casteels, Cindy
    Moons, Lieve
    Van Laere, Koen
    [J]. FRONTIERS IN NEUROSCIENCE, 2019, 13
  • [10] Prevalence of Asymptomatic Carotid Artery Stenosis According to Age and Sex Systematic Review and Metaregression Analysis
    de Weerd, Marjolein
    Greving, Jacoba P.
    de Jong, Anne W. F.
    Buskens, Erik
    Bots, Michiel L.
    [J]. STROKE, 2009, 40 (04) : 1105 - 1113