IN SILICO COMPARISON OF POTENTIALLY SECRETED PROTEINS FROM ENDOTHELIAL COLONY-FORMING CELLS IN ISCHEMIC STROKE AND SICKLE CELL ANEMIA

Júlia Nicoliello Pereira de Castro; Sueli Matilde da Silva Costa; Mirta Tomie Ito; Ana Carolina Camargo; Bruno Batista de Souza; Victor de Haidar e Bertozzo; Thiago Adalton Rosa Rodrigues; Fernando Ferreira Costa; Mônica Barbosa de Melo

Paper Title

Authors

Júlia Nicoliello Pereira de Castro
Sueli Matilde da Silva Costa
Mirta Tomie Ito
Ana Carolina Camargo
Bruno Batista de Souza
Victor de Haidar e Bertozzo
Thiago Adalton Rosa Rodrigues
Fernando Ferreira Costa
Mônica Barbosa de Melo

Modality

Poster

Subject area

RNA and transcriptomics

Publishing Date

08/11/2023

Country of Publishing

Brazil | Brasil

Language of Publishing

Inglês

Paper Page

https://www.even3.com.br/anais/xmeeting2023/642354-in-silico-comparison-of-potentially-secreted-proteins-from-endothelial-colony-forming-cells-in-ischemic-stroke-an

ISBN

978-65-272-0061-1

Keywords

Transcriptomic-based secretome analysis, Ischemic stroke, Sickle cell anemia, Gene expression omnibus.

Summary

Among cerebrovascular alterations of sickle cell anemia (SCA), ischemic stroke (IS) is a classic and severe complication. The endothelial activation has a pivotal role in the vaso-occlusion prior to ischemia, along with hemolysis and thromboinflammation. SCA has a complex pathophysiology, and the identification of relevant genes and pathways more intimately related to IS can be challenging due to the wide variability of phenotypic manifestations observed. We aimed to perform a transcriptomic-based secretome analysis of endothelial colony-forming cells (ECFCs) from SCA patients with IS and compare our findings to a different IS cohort. RNA-Seq data of SCA patients with (n=4) and without (n=4) IS were analyzed by edgeR package in R (FDR <0.01 and Log2FC >|2|). Next, we compared the list of differentially expressed genes (DEGs) with the secretome database of The Human Protein Atlas (HPA) to identify genes related to potentially secreted proteins (PSPs). Finally, we aimed to validate our PSPs - DEGs with the GSE22255 dataset of Gene Expression Omnibus (GEO), containing gene expression data of blood samples from IS patients without SCA: cases (n=20) and controls (n=20). We performed functional enrichment analysis (p <0.05) in the Enrichr tool of common genes in both datasets. We found 2,469 DEGs, of which 204 protein-coding genes are potentially secreted. We compared these PSPs – DEGs with the 542 DEGs of GSE22255. There were 4 genes in common, indicating that these PSPs expressed in endothelial cells may be present in plasma: Tissue Factor Pathway Inhibitor (TFPI, Log2FC = -2.5, FDR = 1.22E-05), Collagen Type XIII Alpha 1 Chain (COL13A1, Log2FC = 2.3, FDR = 2.12E-03), Lymphocyte Antigen 6 Family Member E (LY6E, Log2FC = 3.65, FDR = 2.35E-13), Prostaglandin-Endoperoxide Synthase 1 (PTGS1, Log2FC = 2.47, FDR = 8.43E-07). TFPI is a protease that regulates the tissue factor pathway of blood coagulation, and the levels of this factor in plasma have been related to IS. COL13A1 is one of the chains of nonfibrillar collagens, previously associated with bladder cancer. LY6E has a role in T cell physiology, oncogenesis, and immunological modulation. PTGS1 is an enzyme that catalyzes the conversion of arachidonate to prostaglandin and regulates angiogenesis in endothelial cells. Variants in this gene were related to aspirin resistance in IS and considered a risk factor for IS. In the functional enrichment analysis, pathways such as “Cyclooxygenase pathway”, “Negative regulation of hemostasis”, “Prostaglandin biosynthetic process”, “Extrinsic pathway of fibrin clot formation”, “Synthesis of prostaglandins (PG) and thromboxanes (TX)”, ”Complement and coagulation cascades” and “Platelet activation” were observed. The comparative analysis of our transcriptomic-based secretome data with another IS dataset is a relevant approach to identify genes related to PSPs by endothelial cells that are also present in plasma, providing a better understanding of the molecular pathways involved in the complex pathophysiology of IS in SCA and corroborating to the discovery of new biomarkers.

Title of the Event: X-Meeting / BSB 2023
City of the Event: Curitiba
Title of the Proceedings of the event: X-Meeting presentations
Name of the Publisher: Even3
Means of Dissemination: Meio Digital

How to cite

CASTRO, Júlia Nicoliello Pereira de et al.. IN SILICO COMPARISON OF POTENTIALLY SECRETED PROTEINS FROM ENDOTHELIAL COLONY-FORMING CELLS IN ISCHEMIC STROKE AND SICKLE CELL ANEMIA.. In: X-Meeting presentations. Anais...Curitiba(PR) Campus da indústria, 2023. Available in: https//www.even3.com.br/anais/xmeeting2023/642354-IN-SILICO-COMPARISON-OF-POTENTIALLY-SECRETED-PROTEINS-FROM-ENDOTHELIAL-COLONY-FORMING-CELLS-IN-ISCHEMIC-STROKE-AN. Access in: 19/03/2025