Background
Materials and methods
Microarray data
Data preprocessing and DEGs screening
Functional and pathways enrichment analyses
PPI network and subnetwork of module analyses
MiRNAs-TFs-target regulatory network analyses
Survival analysis
Results
Identification of DEGs
Functional and pathways enrichment analyses
Category | Term | Description | P value | Genes |
---|---|---|---|---|
(a) GO functional analysis for upregulated DEGs | ||||
BP | GO:0001822 | Kidney development | 1.89 × 10− 4 | SULF1, ITGA8, etc |
BP | GO:0043066 | Negative regulation of apoptotic process | 4.92 × 10−3 | GCLC, CD38, etc |
BP | GO:0045779 | Negative regulation of bone resorption | 5.80 × 10−3 | CALCA, CD38, etc |
BP | GO:0000302 | Response to reactive oxygen species | 6.35 × 10−3 | GPX2, GSR, etc |
BP | GO:0038083 | Peptidyl-tyrosine autophosphorylation | 6.82 × 10−3 | FRK, LYN, etc |
BP | GO:0009725 | Response to hormone | 7.81 × 10−3 | GCLC, LYN, etc |
BP | GO:0045892 | Negative regulation of transcription, DNA-templated | 9.56 × 10−3 | CD38, GCLC, etc |
BP | GO:0007169 | Transmembrane receptor protein tyrosine kinase signaling pathway | 1.43 × 10−2 | FRK, LYN, etc |
BP | GO:0002250 | Adaptive immune response | 1.48 × 10−2 | LYN, LAX1, etc |
BP | GO:0050853 | B cell receptor signaling pathway | 1.55 × 10−2 | CD38, LYN, etc |
CC | GO:0005576 | Extracellular region | 1.72 × 10−4 | CER1, C3, etc |
CC | GO:0005615 | Extracellular space | 5.81 × 10−3 | CER1, SELP, etc |
CC | GO:0048471 | Perinuclear region of cytoplasm | 7.73 × 10−3 | SYT4, LYN, etc |
CC | GO:0005886 | Plasma membrane | 9.00 × 10−3 | SYT4, CDCP1, etc |
CC | GO:0070062 | Extracellular exosome | 1.21 × 10−2 | FRK, TSPAN1, etc |
CC | GO:0031234 | Extrinsic component of cytoplasmic side of plasma membrane | 2.85 × 10−2 | FRK, LYN, etc. |
CC | GO:0016942 | Insulin-like growth factor binding protein complex | 2.89 × 10−2 | IGF1, IGFBP5 |
CC | GO:0042567 | Insulin-like growth factor ternary complex | 3.83 × 10−2 | IGF1, IGFBP5 |
CC | GO:0005604 | Basement membrane | 4.16 × 10−2 | MATN2, CCDC80, etc |
CC | GO:0005578 | Proteinaceous extracellular matrix | 4.69 × 10−2 | P3H1, OGN, etc |
MF | GO:0005509 | Calcium ion binding | 2.70 × 10−4 | ME3, SYT4, etc |
MF | GO:0008201 | Heparin binding | 1.08 × 10−3 | OGN, SELP, etc. |
MF | GO:0032403 | Protein complex binding | 4.45 × 10−3 | CALCA, FYB, etc |
MF | GO:0004715 | Non-membrane spanning protein tyrosine kinase activity | 1.06 × 10−2 | FRK, LYN, etc |
MF | GO:0033040 | Sour taste receptor activity | 1.97 × 10−2 | PKD2L1, PKD1L3 |
MF | GO:0004222 | Metalloendopeptidase activity | 2.59 × 10−2 | ADAM28, MME, etc |
MF | GO:0016668 | Oxidoreductase activity, acting on a sulfur group of donors, NAD (P) as acceptor | 3.90 × 10−2 | GSR, TXNRD1 |
MF | GO:0043208 | Glycosphingolipid binding | 3.90 × 10−2 | SELP, LYN |
MF | GO:0008237 | Metallopeptidase activity | 4.63 × 10−2 | ADAM28, MME, etc. |
MF | GO:0000988 | Transcription factor activity, protein binding | 4.85 × 10−2 | HEY1, SMAD3 |
(b) GO analysis for downregulated DEGs | ||||
BP | GO:0007399 | Nervous system development | 2.57 × 10−6 | ZC4H2, PCDHB6, etc |
BP | GO:0007156 | Homophilic cell adhesion via plasma membrane adhesion molecules | 4.09 × 10−6 | CDH7, FAT1, etc |
BP | GO:0007268 | Chemical synaptic transmission | 1.12 × 10−4 | CBLN1, PCDHB6, etc |
BP | GO:0007155 | Cell adhesion | 2.53 × 10−4 | EFNB2, SPOCK1, etc |
BP | GO:0001764 | Neuron migration | 1.39 × 10−3 | ASTN1, RELN, etc |
BP | GO:0007411 | Axon guidance | 8.18 × 10−3 | NEO1, CDH4, etc |
BP | GO:0007416 | Synapse assembly | 1.20 × 10−2 | ADGRL3, PCDHB10, etc |
BP | GO:0051965 | Positive regulation of synapse assembly | 1.26 × 10−2 | LRRN3, LRRN1, |
BP | GO:0016339 | Calcium-dependent cell–cell adhesion via plasma membrane cell adhesion molecules | 2.00 × 10−2 | PCDHB6, PCDHB11, etc |
BP | GO:0045666 | Positive regulation of neuron differentiation | 2.31 × 10−2 | SOX11, MMD, etc |
CC | GO:0005887 | Integral component of plasma membrane | 4.14 × 10−4 | GRIK2, MET, etc |
CC | GO:0045211 | Postsynaptic membrane | 4.08 × 10−3 | CBLN1, ZC4H2, etc |
CC | GO:0005886 | Plasma membrane | 1.17 × 10−2 | GRIK2, FHL1, etc |
CC | GO:0031941 | Filamentous actin | 2.05 × 10−2 | MYO6, FSCN1, etc |
CC | GO:0030424 | Axon | 2.15 × 10−2 | STMN2, CNR1, etc |
CC | GO:0030425 | Dendrite | 3.31 × 10−2 | RELN, GNG3, etc |
CC | GO:0000788 | Nuclear nucleosome | 3.93 × 10−2 | HIST1H2BB, HIST1H3C, etc |
CC | GO:0043204 | Perikaryon | 4.02 × 10−2 | ASTN1, KCNK1, etc |
CC | GO:0034705 | Potassium channel complex | 4.21 × 10−2 | KCNA6, KCNK1 |
CC | GO:0030054 | Cell junction | 4.64 × 10−2 | ZC4H2, GRIK2, etc |
MF | GO:0005509 | Calcium ion binding | 6.10 × 10−3 | CDH7, DGKB, etc |
MF | GO:0032051 | Clathrin light chain binding | 3.60 × 10−2 | NSG1, HMP19 |
MF | GO:0009931 | Calcium-dependent protein serine/threonine kinase activity | 5.00 × 10−2 | CAMK4, DCX |
Term | Description | Count | P value | Key genes |
---|---|---|---|---|
(c) KEGG pathway analysis for downregulated DEGs | ||||
hsa05202 | Transcriptional misregulation in cancer | 6 | 1.64 × 10−3 | HIST1H3J, EYA1, MET, ETV1, HIST1H3C, MEIS1 |
hsa04360 | Axon guidance | 5 | 4.07 × 10−3 | EPHA4, PAK3, EFNB2, MET, DPYSL5 |
hsa05034 | Alcoholism | 5 | 1.29 × 10−2 | HIST1H3J, HIST1H2BB, CAMK4, HIST1H3C, GNG3 |
hsa04723 | Retrograde endocannabinoid signaling | 4 | 1.53 × 10−2 | SLC32A1, GABRG2, CNR1, GNG3 |
hsa05322 | Systemic lupus erythematosus | 4 | 3.20 × 10−2 | HIST1H3J, HIST1H2BB, HIST1H3C, HLA-DQA1 |
PPI network and module analyses
Gene | Degree | Regulate |
---|---|---|
PPI | ||
HIST1H2BB | 11 | Down |
IGF1 | 10 | Up |
PRKAR2B | 9 | Down |
GNG3 | 9 | Down |
GSR | 8 | Up |
LYN | 8 | Up |
MGP | 8 | Up |
CALCA | 7 | Up |
TXNRD1 | 7 | Up |
Module a | ||
GNG3 | 9 | Down |
C3 | 6 | Up |
GRM8 | 5 | Down |
SAA1 | 5 | Up |
CNR1 | 5 | Down |
Term | Description | Count | P value | Key genes |
---|---|---|---|---|
PPI | ||||
GO:0042592 | Homeostatic process | 6 | 5.44 × 10−5 | CALCA, GSR, LYN, IGF1, TXNRD1, GNG3 |
GO:0042325 | Regulation of phosphorylation | 5 | 1.53 × 10−4 | CALCA, PRKAR2B, LYN, IGF1, GNG3 |
GO:0019220 | Regulation of phosphate metabolic process | 5 | 1.78 × 10−4 | CALCA, PRKAR2B, LYN, IGF1, GNG3 |
GO:0051174 | Regulation of phosphorus metabolic process | 5 | 1.78 × 10−4 | CALCA, PRKAR2B, LYN, IGF1, GNG3 |
GO:0009725 | Response to hormone stimulus | 4 | 1.47 × 10−3 | PRKAR2B, LYN, MGP, GNG3 |
GO:0009719 | Response to endogenous stimulus | 4 | 1.96 × 10−3 | PRKAR2B, LYN, MGP, GNG3 |
GO:0019725 | Cellular homeostasis | 4 | 2.92 × 10−3 | CALCA, GSR, TXNRD1, GNG3 |
GO:0043085 | Positive regulation of catalytic activity | 4 | 3.99 × 10−3 | CALCA, PRKAR2B, GNG3, CAP1 |
GO:0001932 | Regulation of protein amino acid phosphorylation | 3 | 5.52 × 10−3 | PRKAR2B, LYN, IGF1 |
GO:0044093 | Positive regulation of molecular function | 4 | 5.58 × 10−3 | CALCA, PRKAR2B, GNG3, CAP1 |
Module a | ||||
GO:0007186 | G-protein coupled receptor protein signaling pathway | 4 | 2.14 × 10−3 | C3, GRM8, CNR1, GNG3 |
GO:0007166 | Cell surface receptor linked signal transduction | 4 | 9.26 × 10−3 | C3, GRM8, CNR1, GNG3 |
GO:0050727 | Regulation of inflammatory response | 2 | 2.23 × 10−2 | C3, SAA1 |
GO:0002526 | Acute inflammatory response | 2 | 2.87 × 10−2 | C3, SAA1 |
GO:0007204 | Elevation of cytosolic calcium ion concentration | 2 | 3.21 × 10−2 | SAA1, GNG3 |
GO:0051480 | Cytosolic calcium ion homeostasis | 2 | 3.44 × 10−2 | SAA1, GNG3 |
GO:0032101 | Regulation of response to external stimulus | 2 | 4.62 × 10−2 | C3, SAA1 |
MiRNAs-TFs-target regulatory network analyses
miRNAs | Genes |
---|---|
miR-126 | ZMPSTE24 |
miR-126 | DACH1 |
miR-126 | EYA1 |
miR-126 | RNF152 |
miR-126 | GRM8 |
miR-126 | ZNF354C |
miR-126 | MYT1 |
miR-126 | PCSK2 |
miR-126 | JPH1 |
miR-126 | TMEM47 |
miR-126 | XPR1 |