Identification of novel genetic biomarkers and treatment targets for arteriosclerosis-related abdominal aortic aneurysm using bioinformatic tools

Niu, Fang; Liu, Zongwei; Liu, Peidong; Pan, Hongrui; Bi, Jiaxue; Luo, Guangze; Chen, Yonghui; Zhang, Xiaoxing; Dai, Xiangchen

doi:10.3934/mbe.2021478

Cited by 2 publications

(3 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Discussionmentioning

confidence: 99%

“…This provides further insights into the differential functions of SPI1 in different disease contexts, which is consistent with the findings of previous studies documenting the overexpression of SPI1 in cardiovascular diseases like myocardial infarction 50 and abdominal aortic aneurysm. 51 Central to the hyperactivated state of CD177 + neutrophils are the genes that form the networks that maintain their biological functions. We conducted high-dimensional weighted gene coexpression network analysis to identify hub genes regulating the immune state or function of CD177 + neutrophils.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers

Beltran,

Lin,

Chang

et al. 2023

Circulation

View full text Add to dashboard Cite

BACKGROUND: Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share similar clinical manifestations, including cardiovascular complications, suggesting similar underlying immunopathogenic processes. Aberrant neutrophil activation may play a crucial role in the shared pathologies of KD and MIS-C; however, the associated pathogenic mechanisms and molecular drivers remain unknown. METHODS: We performed a single-cell meta-analysis of neutrophil activation with 103 pediatric single-cell transcriptomic peripheral blood mononuclear cell data across 9 cohorts, including healthy controls, KD, MIS-C, compared with dengue virus infection, juvenile idiopathic arthritis, and pediatric celiac disease. We used a series of computational analyses to investigate the shared neutrophil transcriptional programs of KD and MIS-C that are linked to systemic damage and cardiac pathologies, and suggested Food and Drug Administration–approved drugs to consider as KD and MIS-C treatment. RESULTS: We meta-analyzed 521 950 high-quality cells. We found that blood signatures associated with risks of cardiovascular events are enriched in neutrophils of KD and MIS-C. We revealed the expansion of CD177 + neutrophils harboring hyperactivated effector functions in both KD and MIS-C, but not in healthy controls or in other viral-, inflammatory-, or immune-related pediatric diseases. KD and MIS-C CD177 + neutrophils had highly similar transcriptomes, marked by conserved signatures and pathways related to molecular damage. We found the induction of a shared neutrophil expression program, potentially regulated by SPI1 (Spi-1 proto-oncogene), which confers enhanced effector functions, especially neutrophil degranulation. CD177 and shared neutrophil expression program expressions were associated with acute stages and attenuated during KD intravenous immunoglobulin treatment and MIS-C recovery. Network analysis identified hub genes that correlated with the high activation of CD177 + neutrophils. Disease-gene association analysis revealed that the CD177 + neutrophil shared neutrophil expression program was associated with the development of coronary and myocardial disorders. Last, we identified and validated TSPO (translocator protein) and S100A12 (S100 calcium-binding protein A12) as main molecular targets, for which the Food and Drug Administration–approved drugs methotrexate, zaleplon, metronidazole, lorazepam, clonazepam, temazepam, and zolpidem, among others, are primary candidates for drug repurposing. CONCLUSIONS: Our findings indicate that CD177 + neutrophils may exert systemic pathological damage contributing to the shared morbidities in KD and MIS-C. We uncovered potential regulatory drivers of CD177 + neutrophil hyperactivation and pathogenicity that may be targeted as a single therapeutic strategy for either KD or MIS-C.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers

Beltran,

Lin,

Chang

et al. 2023

Circulation

View full text Add to dashboard Cite

show abstract

“…Scientists are searching for ways to detect poor prognosis early and to take action to prevent it [6][7][8]. Researchers have been attempting to understand the mechanisms of CRC.…”

Section: Introductionmentioning

confidence: 99%

Construction of a Colorectal Cancer Prognostic Risk Model and Screening of Prognostic Risk Genes Using Machine-Learning Algorithms

Han

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

This study is aimed at constructing a prognostic risk model for colorectal cancer (CRC) using machine-learning algorithms to provide accurate staging and screening of credible prognostic risk genes. We extracted CRC data from GSE126092 and GSE156355 of the Gene Expression Omnibus (GEO) database and datasets from TCGA to analyze the differentially expressed genes (DEGs) using bioinformatics analysis. Among the 330 shared DEGs related to CRC prognosis, we divided the analysis period into different phases and applied univariate COX regression, LASSO, and multivariate COX regression analysis. GO analysis and KEGG analysis revealed that the functions of these DEGs were primarily focused on cell cycle, DNA replication, cell mitosis, and other related functions, and this confirmed our results from a biological perspective. Finally, a prognostic risk model for CRC based on the CHGA, CLU, PLK1, AXIN2, NR3C2, IL17RB, GCG, and AJUBA genes was constructed, and the risk score enabled us to predict the prognosis for CRC. To obtain a comprehensive and accurate model, we used both internal and external evaluations, and the model was able to correctly differentiate patients with CRC into a high-risk group with poor prognosis and a low-risk group with good prognosis. The AUC values of the 3-, 5-, and 10-year survival ROC curves were 0.715, 0.721, and 0.777, respectively, according to the internal evaluation, and the AUC values were 0.606, 0.698, and 0.608, respectively, for the external evaluation using GSE39582 from the GEO database. We determined that CLU, PLK1, and IL17RB could be considered to be independent prognostic factors for CRC with significantly different expression ( P < 0.05 ). Using machine-learning methods, a prognostic risk model comprised of eight genes was constructed. Not only does this model provide improved treatment guidance, but it also provides a novel perspective for analyzing survival conditions at a deeper biological level.

show abstract

Identification of novel genetic biomarkers and treatment targets for arteriosclerosis-related abdominal aortic aneurysm using bioinformatic tools

Cited by 2 publications

References 28 publications

Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers

Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers

Construction of a Colorectal Cancer Prognostic Risk Model and Screening of Prognostic Risk Genes Using Machine-Learning Algorithms

Contact Info

Product

Resources

About