WGCNA combined with GSVA to explore biomarkers of refractory neocortical epilepsy

Zhang, Rui; Chen, Yan; He, Jia; Haiyan, Gou; Zhu, Yongwei; Zhu, Yao

doi:10.1016/j.ibneur.2022.09.010

Cited by 4 publications

(7 citation statements)

References 30 publications

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“…The "GSVA" and "GSEABase" packages were used for analysis, and the "ggpubr" package was used to draw boxplots. 26 Differential expression analysis was performed using the "limma" package with the criteria of jlogFCj > 1 and adjusted p < 0.05. 27 The volcano plot was drawn using common R packages.…”

Section: Evaluation Of Immune Cell Abundance and Differential Gene Ex...mentioning

confidence: 99%

Identification of neutrophil‐related genes and development of a prognostic model for cholangiocarcinoma

Xiong

Wang

et al. 2023

The Journal of Gene Medicine

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BackgroundCholangiocarcinoma is a prevalent gastrointestinal tumor with limited effective early diagnostic methods. The role of neutrophils in the context of cholangiocarcinoma remains largely unexplored.MethodsA comprehensive analysis was performed on a cohort of cholangiocarcinoma samples (TCGA‐CHOL) from the TCGA database to investigate the relationship between cholangiocarcinoma and neutrophils. Methodologies included single‐sample gene set enrichment analysis (ssGSEA), differential expression analysis, weighted gene co‐expression network analysis (WGCNA) and gene set enrichment analysis (GSEA).ResultsThe study identified a significant decrease of neutrophils in cholangiocarcinoma via ssGSEA. WGCNA and differential expression analysis led to the identification of a neutrophil‐related gene module comprised of 1059 genes. Cluster 1, showing a higher proportion of neutrophils, was linked to better survival outcomes. GSEA disclosed downregulation of complement, inflammatory response and interferon response pathways in Cluster 2, hinting at possible cholangiocarcinoma development triggers. A notable upregulation of PD1, PD‐L1 and CTLA4 was observed in Cluster 1, suggesting potential benefits from immunotherapy. A prognostic model was developed based on clinical data and expression levels of three prognostic genes (SOWAHD, TNFAIP8 and EBF3) showing satisfactory discrimination, calibration and clinical benefits. An overexpression of TNFAIP8 in cholangiocarcinoma cells was found, with its knockdown significantly inhibiting cell proliferation and migration.ConclusionsThis study elucidates a neutrophil‐related gene module and prognostic genes, offering insights into the role of neutrophils in cholangiocarcinoma development and progression. It also introduces a clinical prediction model for enhanced prognosis assessment. These findings may lay the groundwork for the development of innovative therapeutic strategies in cholangiocarcinoma treatment.

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Section: Evaluation Of Immune Cell Abundance and Differential Gene Ex...mentioning

confidence: 99%

Identification of neutrophil‐related genes and development of a prognostic model for cholangiocarcinoma

Xiong

Wang

et al. 2023

The Journal of Gene Medicine

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Section: Discussionmentioning

confidence: 99%

“…TPC6AΔ is the first one among the known three initiators in the protein aggregation cascade [ 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. When intracellular WWOX is low or becomes dysfunctional, aggregation of TPC6AΔ starts to occur, followed by polymerization of TIAF1 and SH3GLB2 [ 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. The aggregation complex repeats the polymerization or aggregation process and thereby allows accumulation of more protein aggregates in the brain, so as to cause caspase activation, cytochrome c release, and APP degradation for generation of Aβ [ 44 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…Downregulation of WWOX in the brain may start to occur in middle age, and this leads to spontaneous aggregation of a cascade of intracellular proteins, including TIAF1 (TGFβ-induced antiapoptotic protein) [ 42 , 43 ], TRAPPC6AΔ (trafficking protein particle complex 6A isoform, TPC6AΔ) [ 44 , 45 , 46 , 47 , 48 ], and SH3GLB2 (SH3-domain-containing GRB2-like, endophilin B) [ 5 , 49 , 50 ]. Compared to the wild type, the TPC6AΔ isoform has an internal deletion of 14 amino acids in the N -terminus [ 44 ].…”

Section: Introductionmentioning

confidence: 99%

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Zfra Inhibits the TRAPPC6AΔ-Initiated Pathway of Neurodegeneration

Lin

Shih

Yap

et al. 2022

IJMS

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When WWOX is downregulated in middle age, aggregation of a protein cascade, including TRAPPC6AΔ (TPC6AΔ), TIAF1, and SH3GLB2, may start to occur, and the event lasts more than 30 years, which results in amyloid precursor protein (APP) degradation, amyloid beta (Aβ) generation, and neurodegeneration, as shown in Alzheimer’s disease (AD). Here, by treating neuroblastoma SK-N-SH cells with neurotoxin MPP+, upregulation and aggregation of TPC6AΔ, along with aggregation of TIAF1, SH3GLB2, Aβ, and tau, occurred. MPP+ is an inducer of Parkinson’s disease (PD), suggesting that TPC6AΔ is a common initiator for AD and PD pathogenesis. Zfra, a 31-amino-acid zinc finger-like WWOX-binding protein, is known to restore memory deficits in 9-month-old triple-transgenic (3xTg) mice by blocking the aggregation of TPC6AΔ, SH3GLB2, tau, and amyloid β, as well as inflammatory NF-κB activation. The Zfra4-10 peptide exerted a strong potency in preventing memory loss during the aging of 3-month-old 3xTg mice up to 9 months, as determined by a novel object recognition task (ORT) and Morris water maize analysis. Compared to age-matched wild type mice, 11-month-old Wwox heterozygous mice exhibited memory loss, and this correlates with pT12-WWOX aggregation in the cortex. Together, aggregation of pT12-WWOX may link to TPC6AΔ aggregation for AD progression, with TPC6AΔ aggregation being a common initiator for AD and PD progression.

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“…The relationships between modules and LBD haplotypes are shown with a heatmap. We measured the module membership (mM) and gene significance (GS) of individual genes, and the hub genes in the selected modules with |mM| >0.8 and |GS| >0.2 were screened for further analysis ( 19 , 20 ).…”

Section: Methodsmentioning

confidence: 99%

Identification of key genes and signaling pathways associated with dementia with Lewy bodies and Parkinson's disease dementia using bioinformatics

Sun

et al. 2023

Front. Neurol.

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ObjectiveDementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are collectively known as Lewy body dementia (LBD). Considering the heterogeneous nature of LBD and the different constellations of symptoms with which patients can present, the exact molecular mechanism underlying the differences between these two isoforms is still unknown. Therefore, this study aimed to explore the biomarkers and potential mechanisms that distinguish between PDD and DLB.MethodsThe mRNA expression profile dataset of GSE150696 was acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between 12 DLB and 12 PDD were identified from Brodmann area 9 of human postmortem brains using GEO2R. A series of bioinformatics methods were applied to identify the potential signaling pathways involved, and a protein–protein interaction (PPI) network was constructed. Weighted gene co-expression network analysis (WGCNA) was used to further investigate the relationship between gene co-expression and different LBD subtypes. Hub genes that are strongly associated with PDD and DLB were obtained from the intersection of DEGs and selected modules by WGCNA.ResultsA total of 1,864 DEGs between PDD and DLB were filtered by the online analysis tool GEO2R. We found that the most significant GO- and KEGG-enriched terms are involved in the establishment of the vesicle localization and pathways of neurodegeneration-multiple diseases. Glycerolipid metabolism and viral myocarditis were enriched in the PDD group. A B-cell receptor signaling pathway and one carbon pool by folate correlated with DLB in the results obtained from the GSEA. We found several clusters of co-expressed genes which we designated by colors in our WGCNA analysis. Furthermore, we identified seven upregulated genes, namely, SNAP25, GRIN2A, GABRG2, GABRA1, GRIA1, SLC17A6, and SYN1, which are significantly correlated with PDD.ConclusionThe seven hub genes and the signaling pathways we identified may be involved in the heterogeneous pathogenesis of PDD and DLB.

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WGCNA combined with GSVA to explore biomarkers of refractory neocortical epilepsy

Cited by 4 publications

References 30 publications

Identification of neutrophil‐related genes and development of a prognostic model for cholangiocarcinoma

Identification of neutrophil‐related genes and development of a prognostic model for cholangiocarcinoma

Zfra Inhibits the TRAPPC6AΔ-Initiated Pathway of Neurodegeneration

Identification of key genes and signaling pathways associated with dementia with Lewy bodies and Parkinson's disease dementia using bioinformatics

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