Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs)
Abstract
:1. Introduction
2. Results
2.1. Differentially Expressed Serum Proteins Were Identified through Proteomics in Two Species
2.2. CCM1-Associated Signaling Pathways Were Identified through Pathway Analyses among DEPs in Two Species
2.3. Common Shared CCM1-Associated Signaling Pathways Were Identified in Two Species
2.4. Candidate Serum Circulating Biomarkers Were Identified through Comparative Analysis among Common Shared CCM1-Associated Signaling Pathways in Two Species
3. Discussion
4. Materials and Methods
4.1. fCCM Patient Cohort Recruitment Procedure
4.2. Data Collection
4.3. Biomarker Data Collection from Proteomics
4.4. Biomarker Identification through Pathway Analyses with Bioinformatics Tools
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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(A) | ||
Ontology | Description | Genes Involved |
BP | negative regulation of multicellular organismal process | FN1 APOD PGLYRP2 RBP4 KNG1 APOA2 APCS VTN APOE KLKB1 SERPINF2 APOC3 |
BP | vesicle-mediated transport | APOA2 VTN APOE PCLO APOC3 |
BP | regulation of vesicle-mediated transport | APOA2 VTN APOE PCLO APOC3 |
MF | phospholipid binding | APOE PCLO APOC3 |
BP | regulation of wound healing | KNG1 APCS VTN APOE KLKB1 SERPINF2 |
BP | negative regulation of cellular process | APOD PGLYRP2 RBP4 KNG1 C5 APOA2 APCS APOE APOC3 |
(B) | ||
Ontology | Description | Genes Involved |
BP | Cytokine Production | Thbs1 Serpinf1 B2m |
BP | Regulation of Cytokine Production | Thbs1 Serpinf1 B2m |
BP | Behavior | Thbs1 Serpinf1 B2m |
BP | Negative Regulation of Gene Expression | Thbs1 Pglyrp2 Serpinf1 |
BP | Immune Response | Pglyrp2 Igkv1-135 Kng2 Igkv4-70 APCS Ighv6-6 B2m |
CC | Extracellular region | C8b Pf4 Klkb1 Gpx3 Qsox1 F12 RBP4 Gsn Cd5l F5 Lcat Agt Thbs1 Pglyrp2 Igkv1-135 Serpinf1 Kng2 F13a1 Igkv4-70 APCS Ighv6-6 B2m |
(A) | ||
DO:ID | Description | Gene Symbol |
DOID:6262 | Complement Deficiency | APOA1, C3, C4B, C5, C6, C7, C8A, C8B, CFH, CFHR1 |
DOID:1247 | Blood Coagulation Disease | C3, C4B, C5, CFH, CPB2, F11, F13B, FGA, PROS1, SELL, SERPINA10, SERPIND1, SERPINF2, VWF |
DOID:5844 | Myocardial Infarction | APOA1, APOA4, APOE, C3, C4B, C7, C8A, C8B, CFH, CPB2, F11, F13B, FGA, GSN, ITIH4, LPA, SERPIND1, VWF |
DOID:10871 | Age Related Macular Degeneration | APOE, C3, C5, CFD, CFHR1, SELL, SERPINF1, TF |
DO: 576 | Proteinuria | APOA1, APOA4, APOE, C3, C4B, C5,C6, CFH, CPB2, HPX, LPA, VTN |
DO:1074 | Kidney Failure | AMBP, APOA1, APOA4, APOE, C3, C6, CFH, CPB2, FGA, PROS1, S100A8, SELL, SERPINF1, TFRC, VWF |
(B) | ||
DO: ID | Description | Gene Symbol |
DOID:3393 | Coronary Artery Disease | APOA1, APOA2, APOA4, APOC3, APOC4, APOE, APOM, C3, C7, C8A, C8B, CFH, CPB2, F11, F13B, F5, FGA, GSN, ITIH3, ITH4, LCAT, LPA, LUM, PON3, SELL, SERPIND1, SERPINF2, SERPING1, VTN, VWF |
DOID:626 | Complement Deficiency | APOA1, C3,C5, C6, C7, C8A, C8B, CFH, CFHR1 |
DOID:1074 | Kidney Failure | AMBP, APOA1, APOA4, APOC3, APOE, B2M, C3, C6, CFH, CPB2, F5, FGA, LCAT, PROS1, PTGDS, S100A8, SELL, SERPINF1, TFRC, VWF |
DOID:5844 | Myocardial Infarction | APOA1, APOA4, APOC3, APOE, C3, C7, C8A, C8B, CFH, CPB2, F11, F13B, F5, FGA, GSN, ITIH3, ITIH4, LCAT, LPA, SERPIND1, SERPING1, VWF |
DOID:1247 | Blood Coagulation Disease | C3,C5, CFH, CP, CPB2, F11, F13B, F5, FGA, KLKB1, PROS1, SERPINA10, SERPIND1, SERPINF2, VWF |
DOID:74 | Hematopoietic System Disease | APOE, C3,C5,CA1,CP, CPB2, F11, F13B, F5, FGA, KLKB1, MASP2, SELL, SERPINA10, SERPIND1, SERPINF1, SERPINF2, TF, TFRC, VWF |
(A) | ||
ID | Description | Gene Symbol |
hsa04610 | Complement and coagulation cascades | A2M, C1QA, C1QC, C3, C4BP, C6, C8A, F11, F13B, FGA, MASP2, SERPIND1, SERPINF2, VTN VWF |
hsa05171 | Coronavirus disease—COVID-19 | C1QA, C1QC, C3, C6, C8A, F13B, FGA, MASP2, VWF |
hsa05322 | Systemic lupus erythematosus | C1QA, C1QC, C3, C6, C8A, H2AJ |
hsa05150 | Staphylococcus aureus infection | C1QA, C1QC, C3, KRT9, MASP2 |
hsa05133 | Pertussis | C1QA, C1QC, C3, C4BPB |
hsa04613 | Neutrophil extracellular trap formation | C3, FGA, H2AJ, VWF |
hsa04512 | ECM-receptor interaction | CD44, VTN, VWF |
hsa05142 | Chagas disease | C1QA, C1QC, C3 |
(B) | ||
ID | Description | Gene Symbol |
hsa04610 | Complement and coagulation cascades | C1QA, C1QB, C1QC, C3, C4BPB, C5, C6, C7, C8A, C8B, CFD, CFH, CFHR1, CPB2, F11, F13B, F5, FGA, KLKB1, MASP2, PROS1, SERPIND1, SERPINF2, SERPING1, VTN, VWF |
hsa05171 | Coronavirus disease—COVID-19 | C1QA, C1QB, C1QX, C3, C5, C6, C7, C8A, C8B, CFD, F13B, FGA, IKBKG, MASP2,VWF |
hsa05150 | Staphylococcus aureus infection | C1QA, C1QB, C1QC, C3, C5, CFD,CFH, KRT9, MASP2 |
hsa04979 | Cholesterol metabolism | APOA1, APOA2, APOA4, APOC3, APOE, LCAT, LPA |
hsa05322 | Systemic lupus erythematosus | C1QA, C1QB, C1QC, C3, C5, C6, C7, C8A, C8B, H2AJ |
hsa05133 | Pertussis | C1QA, C1QB, C1QC, C3, C4BPB, C5, SERPING1 |
Gene Symbol | Gene Name | Pathway |
---|---|---|
APCS | Amyloid P Component | Complement and coagulation cascades |
SERPINF1 | Serpin Family F Member 1 | Complement and coagulation cascades |
SERPINF2 | Serpin Family F Member 2 | Complement and coagulation cascades |
THBS1 | Thrombospondin 1 | Complement and coagulation cascades |
VTN | Vitronectin | Complement and coagulation cascades |
FN1 | Fibronectin 1 | Complement and coagulation cascades |
F12 | Coagulation Factor XII | Complement and coagulation cascades |
GSN | Gelsolin | Complement and coagulation cascades |
KLKB1 | Kallikrein B1 | Complement and coagulation cascades |
KNG1 | Kininogen 1 | Complement and coagulation cascades |
KNG2 | Kininogen 2 | Complement and coagulation cascades |
LCAT | Lecithin-Cholesterol Acyltransferase | Cholesterol metabolism |
APOA2 | Apolipoprotein A2 | Lipoprotein metabolism |
APOC3 | Apolipoprotein C3 | Lipoprotein metabolism |
APOD | Apolipoprotein D | Lipoprotein metabolism |
APOE | Apolipoprotein E | Lipoprotein metabolism |
PCLO | Piccolo Presynaptic Cytomatrix Protein | Cytoskeletal matrix |
QSOX1 | Quiescin Sulfhydryl Oxidase 1 | Extracellular matrix |
B2M | β2-Microglobulin | Immunopathways |
RBP4 | Retinol Binding Protein 4 | Membrane transporter |
PGLYRP2 | Peptidoglycan Recognition Protein 2 | N-acetylmuramoyl-l-alanine amidase |
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Croft, J.; Grajeda, B.; Aguirre, L.A.; Abou-Fadel, J.S.; Ellis, C.C.; Estevao, I.; Almeida, I.C.; Zhang, J. Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs). Int. J. Mol. Sci. 2024, 25, 4740. https://doi.org/10.3390/ijms25094740
Croft J, Grajeda B, Aguirre LA, Abou-Fadel JS, Ellis CC, Estevao I, Almeida IC, Zhang J. Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs). International Journal of Molecular Sciences. 2024; 25(9):4740. https://doi.org/10.3390/ijms25094740
Chicago/Turabian StyleCroft, Jacob, Brian Grajeda, Luis A. Aguirre, Johnathan S. Abou-Fadel, Cameron C. Ellis, Igor Estevao, Igor C. Almeida, and Jun Zhang. 2024. "Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs)" International Journal of Molecular Sciences 25, no. 9: 4740. https://doi.org/10.3390/ijms25094740
APA StyleCroft, J., Grajeda, B., Aguirre, L. A., Abou-Fadel, J. S., Ellis, C. C., Estevao, I., Almeida, I. C., & Zhang, J. (2024). Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs). International Journal of Molecular Sciences, 25(9), 4740. https://doi.org/10.3390/ijms25094740