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Published on: November 28, 2015
Exploring the Associations between Alzheimer's Disease and GBM Mediated by Microglia Based on Network Analysis
1Chunlong Zhang, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China, zhangchunlong@hrbmu.edu.cn; Nan Wu, wunan@hrbmu.edu.cn, Yanjun Xu, xuyanjun@hrbmu.edu.cn.
Abstract:
Previous studies have revealed that there existed epidemic associations between Alzheimer's disease (AD) and many types of tumors, however, the inner biological mechanism connecting these diseases was not clear currently. In this study, we explored the transcriptome associations between AD and glioblastoma multiforme (GBM) that both originate in the brain, using microglia as a bridge, from gene and network levels. Firstly, we extracted human scRNA sequencing datasets from Gene Expression Omnibus (GEO) database, and identified differentially expressed genes within microglia after cell annotation. It was observed that there were 11 common genes shared by AD and GBM dys-regulated genes. Next, we utilized DIAMOnD and Flow Centrality algorithms to identify microglia modules and mediating pathways connecting these two diseases based on global network topology. Among these candidate pathways, the mediating genes FURIN and BACE1 (from SPIKN5 to CSNK1A1) were not only related to the formation of amyloid beta plaques that accumulate in the brain of AD patients, but also involved in cancer biology. Furthermore, the biological explorations of mediating pathways connecting AD and GBM modules reveal inflammatory response, lipid metabolism disorder, and cell proliferation terms. Finally, novel signatures for early AD detection as well as risk models for glioma prognosis were identified based on mediating genes involved in these pathways. In conclusion, this study provided a novel network-based strategy for exploring microglia mediation between AD and GBM and identified candidate signatures for disease detection and prognosis.
Insights
This study reveals microglia-mediated pathways linking Alzheimer's disease (AD) and glioblastoma multiforme (GBM). It identifies shared genes and biological processes, offering potential biomarkers for early AD detection and glioma prognosis.
Area of Science:
- Neuroscience
- Oncology
- Genomics
Background:
- Epidemiological links exist between Alzheimer's disease (AD) and various cancers.
- The underlying biological mechanisms connecting AD and brain tumors like glioblastoma multiforme (GBM) remain unclear.
- Microglia, the brain's immune cells, are implicated in both neurodegenerative and oncogenic processes.
Purpose of the Study:
- To investigate the transcriptome associations between AD and GBM using microglia as a central component.
- To identify shared genes and molecular pathways connecting these two brain pathologies at the gene and network levels.
- To discover potential biomarkers for early AD detection and prognostic models for glioma.
Main Methods:
- Analysis of human single-cell RNA sequencing datasets from the Gene Expression Omnibus (GEO) database.
- Identification of differentially expressed genes in microglia for both AD and GBM.
- Application of network analysis algorithms (DIAMOnD, Flow Centrality) to uncover mediating pathways and modules.
- Exploration of biological functions associated with identified mediating pathways.
Main Results:
- 11 common differentially expressed genes were identified between AD and GBM in microglia.
- Key mediating genes, FURIN and BACE1, were found to be involved in both amyloid-beta plaque formation in AD and cancer biology.
- Mediating pathways highlighted roles in inflammatory response, lipid metabolism, and cell proliferation.
- Novel signatures for early AD detection and glioma prognosis risk models were identified.
Conclusions:
- This study presents a novel network-based strategy to understand microglia-mediated connections between AD and GBM.
- Identified genes and pathways offer potential diagnostic and prognostic signatures for these distinct neurological and oncological conditions.
- The findings underscore the critical role of microglia in bridging neurodegeneration and brain cancer.
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