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. 2023 Feb 1:14:1048919.
doi: 10.3389/fgene.2023.1048919. eCollection 2023.

Identification of the core genes in Randall's plaque of kidney stone and immune infiltration with WGCNA network

Affiliations

Identification of the core genes in Randall's plaque of kidney stone and immune infiltration with WGCNA network

Lingyun Yu et al. Front Genet. .

Abstract

Background: Randall's plaque is regarded as the precursor lesion of lithiasis. However, traditional bioinformatic analysis is limited and ignores the relationship with immune response. To investigate the underlying calculi formation mechanism, we introduced innovative algorithms to expand our understanding of kidney stone disease. Methods: We downloaded the GSE73680 series matrix from the Gene Expression Omnibus (GEO) related to CaOx formation and excluded one patient, GSE116860. In the RStudio (R version 4.1.1) platform, the differentially expressed genes (DEGs) were identified with the limma package for GO/KEGG/GSEA analysis in the clusterProfiler package. Furthermore, high-correlated gene co-expression modules were confirmed by the WGCNA package to establish a protein-protein interaction (PPI) network. Finally, the CaOx samples were processed by the CIBERSORT algorithm to anchor the key immune cells group and verified in the validation series matrix GSE117518. Results: The study identified 840 upregulated and 1065 downregulated genes. The GO/KEGG results revealed fiber-related or adhesion-related terms and several pathways in addition to various diseases identified from the DO analysis. Moreover, WGCNA selected highly correlated modules to construct a PPI network. Finally, 16 types of immune cells are thought to participate in urolithiasis pathology and are related to hub genes in the PPI network that are proven significant in the validation series matrix GSE117518. Conclusion: Randall's plaque may relate to genes DCN, LUM, and P4HA2 and M2 macrophages and resting mast immune cells. These findings could serve as potential biomarkers and provide new research directions.

Keywords: CIBERSORT; Randall’s plaque; WGCNA (weighted gene co-expression network analyses); immune infiltration; kidney stone; renal calculi.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of immune infiltration, WG-CNA algorithm and core genes screening of the microarray analysis process.
FIGURE 2
FIGURE 2
(A) Baseline p1 with 1905 DEGs, including 840 upregulated and 1065 downregulated genes. (B) DO analysis involving the top 10 related diseases. (C) All GO analyses for DEGs are divided into BP, CC, and MF parts. (D) KEGG bubble plot of Randall’s plaque pathways.
FIGURE 3
FIGURE 3
(A) Red line represents the reasonable soft power value in WGCNA analysis. (B) Randall’s plaque genes merged into various color modules in the dendrogram, and most genes are clustered in the blue module. (C) Various colored modules show the correlation values and p-values in brackets. (D) Scatter plot shows the degree to which genes belong to the yellow module on the x-axis and the coefficient of gene correlated with Randall’s plaque on the y-axis.
FIGURE 4
FIGURE 4
(A,B) GSEA analysis for the yellow module genes exported from the WGCNA method. (C) Intersected genes of the yellow module and DEGs. (D) Ten colored modules indicate hub genes and two regulatory network clusters of intersected genes.
FIGURE 5
FIGURE 5
(A) CIBERSORT algorithm estimation of the percentages of 22 immune background cells in GSE73680. (B) Heatmap displays immune cell correlation among samples with p-values. (C) Violin plot shows immune cells infiltration statistical difference in normal and RP samples. (D) PCA analysis differentiates normal with RP samples.
FIGURE 6
FIGURE 6
(A-a–A-j) Correlation between 10 hub genes and 22 background immune cells. (B) Ten hub genes located in the main expression sites.
FIGURE 7
FIGURE 7
(A) Differential expression of nine hub genes in GSE117518. (B) Differential genes with significant differences between the normal and RP groups marked with asterisks.

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