Background
Methods
Microarray data
Preprocessing of the raw data
Clustering analysis
GO and KEGG pathway enrichment analysis
Screening of transcription factors (TFs) and tumor-associated genes (TAGs)
Network construction
Results
Clustering analysis
GO and KEGG enrichment analysis
Term | Count | P value | Genes | |
---|---|---|---|---|
Cluster 1 | GO: 0006355~regulation of transcription, DNA-dependent | 8 | 4.53E−02 |
PITX2, MSX2, DLX3, IRX3, ZNF181, SMAD9, DMRT2, ETV4
|
GO: 0051252~regulation of RNA metabolic process | 8 | 5.03E−02 |
PITX2, MSX2, DLX3, IRX3, ZNF181, SMAD9, DMRT2, ETV4
| |
GO: 0016337~cell–cell adhesion | 3 | 9.79E−02 |
REG3A, CLDN1, CDH3
| |
GO: 0030574~collagen catabolic process | 2 | 3.78E−02 |
KLK6, MMP7
| |
GO: 0044243~multicellular organismal catabolic process | 2 | 4.88E−02 |
KLK6, MMP7
| |
GO: 0032963~collagen metabolic process | 2 | 5.25E−02 |
KLK6, MMP7
| |
GO: 0044259~multicellular organismal macromolecule metabolic process | 2 | 5.80E−02 |
KLK6, MMP7
| |
GO: 0044236~multicellular organismal metabolic process | 2 | 6.88E−02 |
KLK6, MMP7
| |
GO: 0042552~myelination | 2 | 7.06E−02 |
KLK6, CLDN1
| |
GO: 0007272~ensheathment of neurons | 2 | 7.77E−02 |
KLK6, CLDN1
| |
Cluster 2 | GO: 0007586~digestion | 3 | 2.69E−02 |
CAPN9, TFF2, TFF1
|
GO: 0002526~acute inflammatory response | 3 | 3.08E−02 |
SERPINA1, C4BPA, LBP
| |
GO: 0010038~response to metal ion | 3 | 5.07E−02 |
XDH, SERPINA1, TFF1
| |
GO: 0045087~innate immune response | 3 | 5.72E−02 |
C4BPA, LBP, DEFB1
| |
GO: 0008544~epidermis development | 3 | 9.41E−02 |
COL17A1, LAMA3, RBP2
| |
Cluster 3 | GO: 0006955~immune response | 30 | 3.03E−15 |
ITGAL, IL16, LY86
|
GO: 0045321~leukocyte activation | 16 | 1.67E−10 |
ITGAL, CD3G, TNFSF4
| |
GO: 0001775~cell activation | 16 | 1.79E−09 |
ITGAL, CD3G, TNFSF4
| |
GO: 0006952~defense response | 16 | 3.00E−05 |
ITGAL, TNFSF4, AIF1
| |
GO: 0042110~T cell activation | 15 | 2.58E−13 |
ITGAL, CD3G, TNFSF4
| |
GO: 0046649~lymphocyte activation | 15 | 1.35E−10 |
ITGAL, CD3G, TNFSF4
| |
GO: 0008283~cell proliferation | 11 | 1.12E−03 |
HHEX, STAT4, DOCK2
| |
GO: 0042127~regulation of cell proliferation | 11 | 5.52E−02 |
HHEX, CORO1A, TNFSF4
| |
GO: 0007610~behavior | 10 | 6.45E−03 |
CORO1A, DOCK2, IL16
| |
GO: 0009611~response to wounding | 10 | 1.37E−02 |
ITGAL, TNFSF4, AIF1
| |
Cluster 4 | GO: 0006334~nucleosome assembly | 9 | 3.17E−08 |
HIST2H2AA3, HIST4H4, HIST1H1E
|
GO: 0031497~chromatin assembly | 9 | 4.19E−08 |
HIST2H2AA3, HIST4H4, HIST1H1E
| |
GO: 0065004~protein-DNA complex assembly | 9 | 5.98E−08 |
HIST2H2AA3, HIST4H4, HIST1H1E
| |
GO: 0034728~nucleosome organization | 9 | 7.10E−08 |
HIST2H2AA3, HIST4H4, HIST1H1E
| |
GO: 0006323~DNA packaging | 9 | 4.24E−07 |
HIST2H2AA3, HIST4H4, HIST1H1E
| |
GO: 0007155~cell adhesion | 18 | 5.34E−07 |
EMCN, NRP1, CCL2
| |
GO: 0022610~biological adhesion | 18 | 5.45E−07 |
EMCN, NRP1, CCL2
| |
GO: 0006333~chromatin assembly or disassembly | 9 | 7.96E−07 |
HIST2H2AA3, HIST4H4, HIST1H1E
| |
GO: 0009611~response to wounding | 14 | 1.26E−05 |
C3AR1, CCL3, IL6
| |
GO: 0001568~blood vessel development | 9 | 9.73E−05 |
VEGFC, EMCN, NRP1
|
Term | Count | P-value | Genes | |
---|---|---|---|---|
Cluster 1 | hsa00980: Metabolism of xenobiotics by cytochrome P450 | 2 | 9.06E−02 |
CYP3A7, ALDH3B2
|
hsa00982: Drug metabolism | 2 | 9.35E−02 |
CYP3A7, ALDH3B2
| |
Cluster 3 | hsa04672: Intestinal immune network for IgA production | 9 | 2.24E−08 |
TNFSF13B, CXCR4, ICOS
|
hsa04514: Cell adhesion molecules (CAMs) | 9 | 4.80E−05 |
ITGAL, SELL, ICOS
| |
hsa04060: Cytokine-cytokine receptor interaction | 9 | 4.66E−03 |
IL2RB, TNFSF4, TNFSF13B
| |
hsa05416: Viral myocarditis | 8 | 6.22E−06 |
ITGAL, MYH11, HLA-DPA1
| |
hsa04062: Chemokine signaling pathway | 7 | 1.14E−02 |
DOCK2, CCL21, CXCR4
| |
hsa05340: Primary immunodeficiency | 6 | 2.37E−05 |
CD3D, ICOS, TNFRSF13B
| |
hsa04640: Hematopoietic cell lineage | 6 | 1.71E−03 |
CD37, CD3G, CD3D
| |
hsa04660: T cell receptor signaling pathway | 6 | 4.63E−03 |
CD3G, CD3D, ICOS
| |
hsa05330: Allograft rejection | 5 | 4.50E−04 |
HLA-DPA1, HLA-DPB1, HLA-DOA
| |
hsa05332: Graft-versus-host disease | 5 | 6.14E−04 |
HLA-DPA1, HLA-DPB1, HLA-DOA
| |
hsa04940: Type I diabetes mellitus | 5 | 8.17E−04 |
HLA-DPA1, HLA-DPB1, HLA-DOA
| |
hsa05320: Autoimmune thyroid disease | 5 | 1.70E−03 |
HLA-DPA1, HLA-DPB1, HLA-DOA
| |
hsa04612: Antigen processing and presentation | 5 | 9.86E−03 |
CD4, HLA-DPA1, HLA-DPB1
| |
hsa05322: Systemic lupus erythematosus | 5 | 1.79E−02 |
HLA-DPA1, HLA-DPB1, HLA-DOA
| |
hsa05310: Asthma | 4 | 3.06E−03 |
HLA-DPA1, HLA-DPB1, HLA-DOA
| |
Cluster 4 | hsa05322: Systemic lupus erythematosus | 9 | 5.81E−07 |
HIST2H2AA3, HIST4H4, HIST1H2BC
|
hsa04670: Leukocyte transendothelial migration | 6 | 1.89E−03 |
HIST2H2AA3, HIST4H4, HIST1H2BC
| |
hsa04514: Cell adhesion molecules (CAMs) | 6 | 3.10E−03 |
PECAM1, CLDN5, CLDN11
| |
hsa04621: NOD-like receptor signaling pathway | 4 | 1.15E−02 |
IL6, CCL2, NFKBIA, NLRP3
| |
hsa04620: Toll-like receptor signaling pathway | 4 | 4.15E−02 |
FOS, CCL3, IL6, NFKBIA
|
Identification of oncogenes, TSGs and TFs amongst the selected genes
TF | TSG | Oncogene | Other | |
---|---|---|---|---|
Cluster 1 | ETV4, MSX2, PITX2, SMAD9 | CUL7 | KLK6 | |
Cluster 2 | CEACAM7, DEFB1, MUC1, SLC26A3 | |||
Cluster 3 | EOMES, HEY2, HHEX, MEF2C, POU2AF1, STAT4, TCF21, TCF4 | AIM2, BEX2, MAP4K1, PEG3, PRICKLE1, PYHIN1, TCF4 | EVI2B | |
Cluster 4 | ATF3, DBP, HAND1, KLF2, MAFB, SOX18 | ZFP36 | FOS | CCL2, MAFB, RGS2, RHOB |
Screening of miRNAs
MiRNA | Count | P-value | Gene | |
---|---|---|---|---|
Cluster 1 | hsa-miR-382 | 3 | 5.77E−03 |
CLDN1, DLX3, IRX3
|
hsa-miR-217 | 4 | 1.11E−02 |
DMRT2, MSX2, SMAD9, VSNL1
| |
hsa-miR-21 | 2 | 4.80E−02 |
PITX2, VSNL1
| |
Cluster 3 | hsa-miR-935 | 2 | 1.69E−02 |
EOMES, RELN
|
hsa-miR-1184 | 2 | 2.90E−02 |
TCF4, HEY2
| |
hsa-miR-326 | 6 | 3.02E−02 |
TCF4, C16orf45, HLA-DOA, PKIA, PTGIS, SPOCK1
| |
hsa-miR-496 | 5 | 3.45E−02 |
RASGRP3, ARHGEF6, MOXD1, PEG3, PTGIS
| |
hsa-miR-330-5p | 5 | 4.22E−02 |
TCF4, C16orf45, HLA-DOA, PKIA, SPOCK1
| |
Cluster 4 | hsa-miR-338-5p | 6 | 8.35E−04 |
EBF3, KLF2, LDB2, NRP1, SLIT3, VEGFC
|
hsa-miR-656 | 4 | 6.96E−03 |
COLEC12, DUSP1, TEK, ZFP36
| |
hsa-miR-30d | 9 | 1.08E−02 |
CYYR1, EBF3, EMCN, GFPT2, NRP1, RGS2, RHOB, RRAD, ZNF521
| |
hsa-miR-30b | 9 | 1.10E−02 |
CYYR1, EBF3, EMCN, GFPT2, NRP1, RGS2, RHOB, RRAD, ZNF521
| |
hsa-miR-30a | 9 | 1.11E−02 |
CYYR1, EBF3, EMCN, GFPT2,NRP1, RGS2, RHOB, RRAD, ZNF521
| |
hsa-miR-30c | 9 | 1.12E−02 |
CYYR1, EBF3, EMCN, GFPT2, NRP1, RGS2, RHOB, RRAD, ZNF521
| |
hsa-miR-30e | 9 | 1.12E −02 |
CYYR1, EBF3, EMCN, GFPT2, NRP1, RGS2, RHOB, RRAD, ZNF521
| |
hsa-miR-300 | 10 | 2.79E−02 |
EBF3, IER5, LDB2, MMRN1, NFKBIA, NRP1, SELE, TEK, ZFP36, ZNF521
| |
hsa-miR-27a | 6 | 4.69E−02 |
CDH5, EBF3, GEM, GFPT2, RGS1, VEGFC
| |
hsa-miR-27b | 6 | 4.73E−02 |
CDH5, EBF3, GEM, GFPT2, RGS1, VEGFC
|