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Identification of key target genes and pathway analysis in nonalcoholic fatty liver disease via integrated bioinformatics analysis

X. Chen
X. Chen
, 
L. Zhang
L. Zhang
, 
Y. Wang
Y. Wang
, 
R. Li
R. Li
, 
M. Yang
M. Yang
 oraz 
L. Gao
L. Gao
   | 01 mar 2023
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Article Category: Original Article
Data publikacji: 01 mar 2023
Zakres stron: 25 - 34
DOI: https://doi.org/10.2478/bjmg-2022-0006
© 2022 Chen X., Zhang L., Wang Y., Li R., Yang M., Gao L., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1

The hierarchically clustering analysis of screened differentially expressed RNAs (DERs). Left: log2FC-log10 (FDR) volcano map for GSE83452 using the significant DERs. Blue and red dots indicate significant DERs. The horizontally dashed line indicates FDR < 0.05. Two vertical lines indicate |Log2FC| > 0.5. A: Baseline time points; B: 1-year follow-up time points. Right: Two-way hierarchically clustered heat map for GSE83452 using the DERs. Red: upregulated DERs. Blue: downregulated DERs. C: Baseline time points; D: 1-year follow-up time points.
The hierarchically clustering analysis of screened differentially expressed RNAs (DERs). Left: log2FC-log10 (FDR) volcano map for GSE83452 using the significant DERs. Blue and red dots indicate significant DERs. The horizontally dashed line indicates FDR < 0.05. Two vertical lines indicate |Log2FC| > 0.5. A: Baseline time points; B: 1-year follow-up time points. Right: Two-way hierarchically clustered heat map for GSE83452 using the DERs. Red: upregulated DERs. Blue: downregulated DERs. C: Baseline time points; D: 1-year follow-up time points.

Figure 2

Authentication of overlapping DERs in the GSE83452 datasets via Venn diagrams software. Blue represents DERs of the baseline time points group. Yellow represents DERs of the 1-year follow-up time points group.
Authentication of overlapping DERs in the GSE83452 datasets via Venn diagrams software. Blue represents DERs of the baseline time points group. Yellow represents DERs of the 1-year follow-up time points group.

Figure 3

The lncRNA–miRNA–mRNA ceRNA network. Squares, triangles, and circles represent lncRNA, miRNA, and mRNA, respectively. Green and red dots indicate the significantly downregulated DERs at both baseline and 1-year follow-up time points, and the white dots indicate DERs whose expression difference direction has changed.
The lncRNA–miRNA–mRNA ceRNA network. Squares, triangles, and circles represent lncRNA, miRNA, and mRNA, respectively. Green and red dots indicate the significantly downregulated DERs at both baseline and 1-year follow-up time points, and the white dots indicate DERs whose expression difference direction has changed.

Figure 4

Gene–drug connection network. Squares represent drug molecules, circles represent genes, and green and red dots represent the significantly downregulated DERs at both baseline and 1-year follow-up time points.
Gene–drug connection network. Squares represent drug molecules, circles represent genes, and green and red dots represent the significantly downregulated DERs at both baseline and 1-year follow-up time points.

Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the differentially expressed RNAs (DERs).

Category Term Count P-Value Genes
Biology Process GO:0006935~chemotaxis 8 3.110E-04 MAP2K1, CXCL9, AMOT, etc
GO:0006636~unsaturated fatty acid biosynthetic process 4 4.770E-04 FADS1, SCD, FADS2, etc
GO:0007267~cell-cell signaling 10 1.513E-03 SH2D1A, ADM, FADS1, etc
GO:0007568~aging 8 1.848E-03 TYMS, ADM, APOD, etc
GO:0007166~cell surface receptor signaling pathway 10 2.538E-03 MARCO, PRLR, TSPAN3, etc
GO:0055114~oxidation-reduction process 15 4.070E-03 KDM6A, HSD17B2, PYROXD2, etc
GO:0016337~single organismal cell-cell adhesion 6 4.312E-03 MPZL2, PKHD1, FAT1, etc
GO:0006629~lipid metabolic process 7 6.425E-03 APOD, PLIN1, APOF, etc
GO:0070098~chemokine-mediated signaling pathway 5 6.698E-03 TFF2, CXCL9, ACKR3, etc
GO:0032496~response to lipopolysaccharide 7 7.895E-03 ADM, DUSP10, CXCL9, etc
GO:0010508~positive regulation of autophagy 4 8.546E-03 RNF152, FOXO1, TRIM22, etc
GO:0035338~long-chain fatty-acyl-CoA biosynthetic process 4 9.779E-03 SCD, FASN, ELOVL6, ACSL5
GO:0006915~apoptotic process 13 1.716E-02 PEG10, RASSF6, LITAF, etc
GO:0002250~adaptive immune response 6 2.033E-02 SH2D1A, EOMES, CD1C, etc
GO:0006959~humoral immune response 4 2.223E-02 SH2D1A, BST1, LTF, CD28
GO:0006968~cellular defense response 4 2.767E-02 SH2D1A, CXCL9, LBP, etc
GO:0060326~cell chemotaxis 4 3.124E-02 CXCL9, CCL5, DOCK4, etc
GO:0045766~positive regulation of angiogenesis 5 3.346E-02 ADM, LRG1, RHOB, etc
GO:0032868~response to insulin 4 3.374E-02 ADM, INSIG2, FADS1, PCK1
GO:0008203~cholesterol metabolic process 4 3.504E-02 INSIG2, APOF, LEPR, ERLIN1
GO:0001889~liver development 4 4.331E-02 COBL, ONECUT1, DBP, RPGRIP1L
GO:0006954~inflammatory response 9 4.788E-02 LXN, AOX1, LYZ, etc
KEGG Pathway hsa01212:Fatty acid metabolism 6 2.300E-04 FADS1, SCD, FASN, etc
hsa03320:PPAR signaling pathway 6 1.090E-03 PLIN1, SCD, FADS2, etc
hsa04620:Toll-like receptor signaling pathway 7 1.479E-03 CTSK, MAP2K1, CXCL9, etc
hsa01040:Biosynthesis of unsaturated fatty acids 4 2.350E-03 FADS1, SCD, FADS2, ELOVL6
hsa04640:Hematopoietic cell lineage 6 3.475E-03 CR1, CD2, CD1C, etc
hsa04152:AMPK signaling pathway 6 1.465E-02 LEPR, SCD, FASN, etc
hsa04668:TNF signaling pathway 5 3.695E-02 MAP2K1, IL15, CREB3L3, etc
hsa00760:Nicotinate and nicotinamide metabolism 3 4.529E-02 BST1, ENPP3, AOX1
hsa04060:Cytokine-cytokine receptor interaction 7 4.659E-02 PRLR, LEPR, CXCL9, etc

Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the mRNA in the ceRNA regulatory network.

Category Term Count P-Value Genes
Biology Process GO:0008610~lipid biosynthetic process 12 1.15E-06 PRLR, ADM, ISPD, etc
GO:0008202~steroid metabolic process 9 1.26E-05 PRLR, INSIG2, ADM, etc
GO:0006694~steroid biosynthetic process 6 9.34E-05 PRLR, ADM, FDPS, etc
GO:0006633~fatty acid biosynthetic process 5 8.64E-04 FADS1, SCD, FASN, etc
GO:0046649~lymphocyte activation 6 4.38E-03 PRLR, EOMES, IL15, etc
GO:0016053~organic acid biosynthetic process 5 9.79E-03 FADS1, SCD, FASN, etc
GO:0046394~carboxylic acid biosynthetic process 5 9.79E-03 FADS1, SCD, FASN, etc
GO:0045321~leukocyte activation 6 9.84E-03 PRLR, EOMES, IL15, etc
GO:0006355~regulation of transcription, DNA-dependent 18 1.19E-02 CAMTA2, MAP2K1, LITAF, etc
GO:0030334~regulation of cell migration 5 1.31E-02 MAP2K1, CLIC4, AMOT, etc
GO:0051252~regulation of RNA metabolic process 18 1.47E-02 CAMTA2, MAP2K1, etc
GO:0007267~cell-cell signaling 9 1.52E-02 ADM, FADS1, FAT1, etc
GO:0051094~positive regulation of developmental process 6 1.71E-02 MAP2K1, EOMES, AMOT, etc
GO:0001775~cell activation 6 1.93E-02 PRLR, EOMES, IL15, etc
GO:0040012~regulation of locomotion 5 2.00E-02 MAP2K1, CLIC4, AMOT, etc
GO:0051270~regulation of cell motion 5 2.04E-02 MAP2K1, CLIC4, AMOT, etc
GO:0009719~response to endogenous stimulus 7 2.19E-02 MAP2K1, ADM, FADS1, etc
GO:0006631~fatty acid metabolic process 5 2.21E-02 FADS1, SCD, FASN, etc
GO:0045860~positive regulation of protein kinase activity 5 3.23E-02 PRLR, MAP2K1, CD24, etc
GO:0060429~epithelium development 5 3.42E-02 STX2, MAP2K1, RPGRIP1L, etc
GO:0033674~positive regulation of kinase activity 5 3.61E-02 PRLR, MAP2K1, CD24, etc
GO:0051347~positive regulation of transferase activity 5 4.06E-02 PRLR, MAP2K1, CD24, etc
GO:0001568~blood vessel development 5 4.33E-02 LEPR, FOXO1, AMOT, etc
GO:0051254~positive regulation of RNA metabolic process 7 4.51E-02 CAMTA2, MAP2K1, CSRNP1, etc
GO:0001944~vasculature development 5 4.66E-02 LEPR, FOXO1, AMOT, etc
GO:0009725~response to hormone stimulus 6 4.80E-02 MAP2K1, ADM, FADS1, etc
GO:0030030~cell projection organization 6 4.84E-02 STX2, MAP2K1, ADM, etc
GO:0007243~protein kinase cascade 6 4.94E-02 PRLR, MAP2K1, DUSP10, etc
KEGG Pathway hsa01040:Biosynthesis of unsaturated fatty acids 4 2.39E-05 FADS1, SCD, FADS2, ELOVL6
hsa00900:Terpenoid backbone biosynthesis 2 8.23E-03 FDPS, MVK
hsa00534:Heparan sulfate biosynthesis 2 1.38E-02 EXT1, HS3ST3B1
hsa04910:Insulin signaling pathway 3 1.79E-02 MAP2K1, FASN, FOXO1
hsa04060:Cytokine-cytokine receptor interaction 4 1.86E-02 PRLR, LEPR, IL15, CXCL10
hsa04010:MAPK signaling pathway 4 1.93E-02 MAP2K1, DUSP10, MAP3K13, FGF2
hsa04630:Jak-STAT signaling pathway 3 2.21E-02 PRLR, LEPR, IL15
hsa05200:Pathways in cancer 4 2.87E-02 MAP2K1, FZD1, FOXO1, FGF2
hsa03320:PPAR signaling pathway 2 3.28E-02 SCD, FADS2
eISSN:
1311-0160
Język:
Angielski
Częstotliwość wydawania:
2 razy w roku
Dziedziny czasopisma:
Medicine, Basic Medical Science, other
Kanał RSS czasopisma