Bioinformatics analysis of differentially co-expressed genes in peripheral blood and hippocampal tissue of patients with Alzheimer’s disease

Zhong Yishi; Wu Yinru; Gao Jian; Song Weiqi; Chen Peiliang; Chen Ziting; Wu Xianbo

doi:10.13406/j.cnki.cyxb.003383

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Bioinformatics analysis of differentially co-expressed genes in peripheral blood and hippocampal tissue of patients with Alzheimer’s disease

Bioinformatics analysis | 更新时间：2025-10-22

- Bioinformatics analysis of differentially co-expressed genes in peripheral blood and hippocampal tissue of patients with Alzheimer’s disease
- Journal of Chongqing Medical University Vol. 48, Issue 12, Pages: 1507-1513(2023)
- 作者机构：
  
  南方医科大学公共卫生学院流行病学系，广州　510515
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003383
  CLC： R749
- Received：16 September 2023，
  
  Revised：2023-11-17，
  
  Accepted：02 December 2023，
  
  Published：28 December 2023
- 稿件说明：
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钟逸诗,吴茵如,高健,等.阿尔茨海默病患者外周血和海马组织共表达差异基因的生物信息学分析[J].重庆医科大学学报,2023,48(12):1507-1513.

Zhong Yishi,Wu Yinru,Gao Jian,et al.Bioinformatics analysis of differentially co-expressed genes in peripheral blood and hippocampal tissue of patients with Alzheimer’s disease[J].Journal of Chongqing Medical University,2023,48(12):1507-1513.
钟逸诗,吴茵如,高健,等.阿尔茨海默病患者外周血和海马组织共表达差异基因的生物信息学分析[J].重庆医科大学学报,2023,48(12):1507-1513. DOI： 10.13406/j.cnki.cyxb.003383.

Zhong Yishi,Wu Yinru,Gao Jian,et al.Bioinformatics analysis of differentially co-expressed genes in peripheral blood and hippocampal tissue of patients with Alzheimer’s disease[J].Journal of Chongqing Medical University,2023,48(12):1507-1513. DOI： 10.13406/j.cnki.cyxb.003383.

摘要

目的

基于生物信息学筛选阿尔茨海默病（Alzheimer's disease，AD）患者外周血和海马组织中有共同表达趋势的差异基因，为AD的诊断、治疗靶点的筛选提供新的思路。

方法

从基因表达综合数据库（Gene Expression Omnibus，GEO）下载关于AD的数据集GSE97760（9例AD、10例健康对照）、GSE5281（10例AD、13例健康对照）进行生物信息学分析。分别筛选AD患者外周血和海马组织的差异表达基因（differentially expressed genes，DEGs），并确定2个数据集中有共同表达趋势的DEGs。对共表达DEGs进行基因本体论（Gene Ontology，GO）富集分析和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路分析，构建蛋白互作（protein-protein interaction，PPI）网络进一步筛选关键基因，并对关键基因进行验证。

结果

基于对2个GEO数据集的综合分析，共筛选出669个共表达DEGs，包括64个上调DEGs、605个下调DEGs，GO和KEGG分析分别揭示了174个关键条目、40个关键通路，主要在RNA聚合酶的转录调控、神经胶质瘤通路等方面显著富集。通过PPI网络进一步筛选出10个与AD相关的关键基因

TP53、PTEN、HNRNPC、EIF4G1、SF3B1、SRSF11、PIK3R1、RBM39、LUC7L3、RBM25

，其中

PTEN、HNRNPC、SF3B1、PIK3R1、LUC7L3

在数据集GSE48350中得到了验证。

结论

本研究筛选得出的5个值得进一步研究的关键基因（

PTEN、HNRNPC、SF3B1、PIK3R1、LUC7L3

），可作为AD诊断的潜在生物标志物。

Abstract

Objective

To determine differentially co-expressed genes in the peripheral blood and hippocampal tissue of patients with Alzheimer’s disease（AD） by bioinformatics analysis，and to provide new ideas for AD diagnosis and therapeutic target selection.

Methods

We downloaded the AD-associated datasets GSE97760（9 cases of AD and 10 healthy controls） and GSE5281（10 cases of AD and 13 healthy controls） from the Gene Expression Omnibus（GEO） database for bioinformatics analysis. We selected differentially expressed genes（DEGs） in the peripheral blood and hippocampal tissues of patients with AD separately；identified the co-expressed DEGs in the two datasets； then performed Gene Ontology（GO） analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway analysis on the co-expressed DEGs；and constructed a protein-protein interaction（PPI） network to further determine the key genes，followed by validation.

Results

Through the comprehensive analysis of the two GEO datasets，a total of 669 co-expressed DEGs were selected，including 64 up-regulated DEGs and 605 down-regulated DEGs. The GO and KEGG analyses selected 174 key items and

40 key pathways，respectively，which were significantly enriched mainly in the transcriptional regulation of RNA polymerase and glioma pathway. The PPI network determined 10 key AD-related genes：

TP53

，

PTEN

，

HNRNPC

，

EIF4G1

，

SF3B1

，

SRSF11

，

PIK3R1

，

RBM39

，

LUC7L3

，and

RBM25

，of which

PTEN

，

HNRNPC

，

SF3B1

，

PIK3R1

，and

LUC7L3

were validated in the dataset GSE48350.

Conclusion

The five key genes（

PTEN

，

HNRNPC

，

SF3B1

，

PIK3R1

，and

LUC7L3

） selected in this study may serve as potential biomarkers for AD diagnosis，which deserve further research.

关键词

Keywords

references

Zhang LX ， Long JY ， Jiang WS ， et al . Trends in chronic kidney disease in China [J ] . N Engl J Med ， 2016 ， 375 （ 9 ）： 905 - 906 ．

Gupta Y ， Lama RK ， Kwon GR ， et al . Prediction and classification of Alzheimer’s disease based on combined features from apolipoprotein-E genotype，cerebrospinal fluid，MR，and FDG-PET imaging biomarkers [J ] . Front Comput Neurosci ， 2019 ， 13 ： 72 ．

Lisman J ， Buzsáki G ， Eichenbaum H ， et al . Publisher correction：viewpoints：how the hippocampus contributes to memory，navigation and cognition [J ] . Nat Neurosci ， 2018 ， 21 （ 7 ）： 1018 ．

Gns HS ， Rajalekshmi SG ， Burri RR . Revelation of pivotal genes pertinent to Alzheimer’s pathogenesis：a methodical evaluation of 32 GEO datasets [J ] . J Mol Neurosci ， 2022 ， 72 （ 2 ）： 303 - 322 ．

Ritchie ME ， Phipson B ， Wu D ， et al . Limma powers differential expression analyses for RNA-sequencing and microarray studies [J ] . Nucleic Acids Res ， 2015 ， 43 （ 7 ）： e47 ．

Sherman BT ， Hao M ， Qiu J ， et al . DAVID：a web server for functional enrichment analysis and functional annotation of gene lists（2021 update） [J ] . Nucleic Acids Res ， 2022 ， 50 （ W1 ）： W216 - W221 ．

Szklarczyk D ， Franceschini A ， Wyder S ， et al . STRING v10：protein-protein interaction networks，integrated over the tree of life [J ] . Nucleic Acids Res ， 2015 ， 43 （ Database issue ）： D447 - D452 ．

Chin CH ， Chen SH ， Wu HH ， et al . CytoHubba：identifying hub objects and sub-networks from complex interactome [J ] . BMC Syst Biol ， 2014 ， 8 （ Suppl 4 ）： S11 ．

Yu CX ， Li S ， Whorton AR . Redox regulation of PTEN by S-nitrosothiols [J ] . Mol Pharmacol ， 2005 ， 68 （ 3 ）： 847 - 854 ．

Heras-Sandoval D ， Pérez-Rojas JM ， Hernández-Damián J ， et al . The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration [J ] . Cell Signal ， 2014 ， 26 （ 12 ）： 2694 - 2701 ．

Chang N ， El-Hayek YH ， Gomez E ， et al . Phosphatase PTEN in neuronal injury and brain disorders [J ] . Trends Neurosci ， 2007 ， 30 （ 11 ）： 581 - 586 ．

Backman S ， Stambolic V ， Mak T . PTEN function in mammalian cell size regulation [J ] . Curr Opin Neurobiol ， 2002 ， 12 （ 5 ）： 516 - 522 ．

Gary DS ， Mattson MP . PTEN regulates Akt kinase activity in hippocampal neurons and increases their sensitivity to glutamate and apoptosis [J ] . Neuromolecular Med ， 2002 ， 2 （ 3 ）： 261 - 269 ．

Griffin RJ ， Moloney A ， Kelliher M ， et al . Activation of Akt/PKB，increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer’s disease pathology [J ] . J Neurochem ， 2005 ， 93 （ 1 ）： 105 - 117 ．

Rickle A ， Bogdanovic N ， Volkmann I ， et al . PTEN levels in Alzheimer’s disease medial temporal cortex [J ] . Neurochem Int ， 2006 ， 48 （ 2 ）： 114 - 123 ．

Raj T ， Li YI ， Wong G ， et al . Integrative transcriptome analyses of the aging brain implicate altered splicing in Alzheimer’s disease susceptibility [J ] . Nat Genet ， 2018 ， 50 （ 11 ）： 1584 - 1592 ．

Lee EK ， Kim HH ， Kuwano Y ， et al . hnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies [J ] . Nat Struct Mol Biol ， 2010 ， 17 （ 6 ）： 732 - 739 ．

Mukherjee S ， Singh N ， Sengupta N ， et al . Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78，PHB and hnRNPC through ER stress [J ] . Cell Death Dis ， 2017 ， 8 （ 1 ）： e2556 ．

Tang YQ ， Miao M ， Han SY ， et al . Prognostic value and clinical feature of SF3B1 mutations in myelodysplastic syndromes：a meta-analysis [J ] . Crit Rev Oncol Hematol ， 2019 ， 133 ： 74 - 83 ．

Vanhaesebroeck B ， Stephens L ， Hawkins P . PI3K signalling：the path to discovery and understanding [J ] . Nat Rev Mol Cell Biol ， 2012 ， 13 （ 3 ）： 195 - 203 ．

Curtis D ， Bakaya K ， Sharma L ， et al . Weighted burden analysis of exome-sequenced late-onset Alzheimer’s cases and controls provides further evidence for a role for PSEN 1 and suggests involvement of the PI3K/Akt/GSK-3β and Wnt signalling pathways [J ] . Ann Hum Genet ， 2020 ， 84 （ 3 ）： 291 - 302 ．

Qi PF ， Li J ， Gao SC ， et al . Network pharmacology-based and experimental identification of the effects of quercetin on Alzheimer’s disease [J ] . Front Aging Neurosci ， 2020 ， 12 ： 589588 ．

Malouf GG ， Su XP ， Yao H ， et al . Next-generation sequencing of translocation renal cell carcinoma reveals novel RNA splicing partners and frequent mutations of chromatin-remodeling genes [J ] . Clin Cancer Res ， 2014 ， 20 （ 15 ）： 4129 - 4140 ．

Chin LS ， Singh SK ， Wang Q ， et al . Identification of okadaic-acid-induced genes by mRNA differential display in glioma cells [J ] . J Biomed Sci ， 2000 ， 7 （ 2 ）： 152 - 159 ．

Tang RH ， Liu HY . Identification of temporal characteristic networks of peripheral blood changes in Alzheimer’s disease based on weighted gene co-expression network analysis [J ] . Front Aging Neurosci ， 2019 ， 11 ： 83 ．

Bishof I ， Dammer EB ， Duong DM ， et al . RNA-binding proteins with basic-acidic dipeptide（BAD） domains self-assemble and aggregate in Alzheimer’s disease [J ] . J Biol Chem ， 2018 ， 293 （ 28 ）： 11047 - 11066 ．

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