Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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Center for Computational Systems Medicine
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Gene summary

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Malignant transformation analysis

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Malignant transformation related pathway analysis

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Cell-cell communication analysis

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Single-cell gene regulatory network inference analysis

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Somatic mutation of malignant transformation related genes

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Related drugs of malignant transformation related genes

Gene: TNFAIP3

Gene summary for TNFAIP3

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

TNFAIP3

Gene ID

7128

Gene nameTNF alpha induced protein 3
Gene AliasA20
Cytomap6q23.3
Gene Typeprotein-coding
GO ID

GO:0000079

UniProtAcc

P21580


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Malignant transformation analysis

check button Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells
check button Malignant transformation involving gene list.
Entrez IDSymbolReplicatesSpeciesOrganTissueAdj P-valueLog2FCMalignancy
7128TNFAIP3CA_HPV_3HumanCervixCC4.29e-05-3.50e-010.0414
7128TNFAIP3HSIL_HPV_1HumanCervixHSIL_HPV2.25e-05-5.14e-010.0116
7128TNFAIP3HSIL_HPV_2HumanCervixHSIL_HPV1.42e-14-5.80e-010.0208
7128TNFAIP3N_HPV_2HumanCervixN_HPV1.38e-033.37e-01-0.0131
7128TNFAIP3CCI_3HumanCervixCC1.02e-02-6.00e-010.516
7128TNFAIP3CCII_1HumanCervixCC1.24e-07-7.05e-010.3249
7128TNFAIP3TumorHumanCervixCC7.02e-16-4.63e-010.1241
7128TNFAIP3sample3HumanCervixCC5.99e-09-3.58e-010.1387
7128TNFAIP3H2HumanCervixHSIL_HPV1.70e-05-4.43e-010.0632
7128TNFAIP3T1HumanCervixCC3.92e-052.14e-010.0918
7128TNFAIP3T3HumanCervixCC3.73e-10-3.45e-010.1389
7128TNFAIP3AEH-subject1HumanEndometriumAEH1.78e-145.96e-01-0.3059
7128TNFAIP3AEH-subject2HumanEndometriumAEH3.95e-022.91e-01-0.2525
7128TNFAIP3AEH-subject3HumanEndometriumAEH1.05e-022.51e-01-0.2576
7128TNFAIP3AEH-subject4HumanEndometriumAEH3.86e-279.07e-01-0.2657
7128TNFAIP3AEH-subject5HumanEndometriumAEH1.40e-328.87e-01-0.2953
7128TNFAIP3EEC-subject1HumanEndometriumEEC3.69e-104.81e-01-0.2682
7128TNFAIP3EEC-subject2HumanEndometriumEEC8.81e-124.29e-01-0.2607
7128TNFAIP3EEC-subject3HumanEndometriumEEC5.40e-237.03e-01-0.2525
7128TNFAIP3EEC-subject4HumanEndometriumEEC1.60e-328.79e-01-0.2571
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
CervixThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.CC: Cervix cancer
HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
N_HPV: HPV-infected normal cervix
EndometriumThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.AEH: Atypical endometrial hyperplasia
EEC: Endometrioid Cancer
EsophagusThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.ESCC: Esophageal squamous cell carcinoma
HGIN: High-grade intraepithelial neoplasias
LGIN: Low-grade intraepithelial neoplasias
GCThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.CAG: Chronic atrophic gastritis
CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
CSG: Chronic superficial gastritis
GC: Gastric cancer
SIM: Severe intestinal metaplasia
WIM: Wild intestinal metaplasia
LiverThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.HCC: Hepatocellular carcinoma
NAFLD: Non-alcoholic fatty liver disease
Oral CavityThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.EOLP: Erosive Oral lichen planus
LP: leukoplakia
NEOLP: Non-erosive oral lichen planus
OSCC: Oral squamous cell carcinoma
ProstateThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.BPH: Benign Prostatic Hyperplasia
SkinThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.AK: Actinic keratosis
cSCC: Cutaneous squamous cell carcinoma
SCCIS:squamous cell carcinoma in situ
ThyroidThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.ATC: Anaplastic thyroid cancer
HT: Hashimoto's thyroiditis
PTC: Papillary thyroid cancer
∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

check buttonFind out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer
check button Figure of enriched GO biological processes.
TissueDisease StageEnriched GO biological Processes
ColorectumADGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
ColorectumSERGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
ColorectumMSSGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
ColorectumMSI-HGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
ColorectumFAPGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
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check button Enriched GO biological processes.
GO IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustCount
GO:004232626SkincSCCnegative regulation of phosphorylation137/4864385/187231.63e-051.99e-04137
GO:000193326SkincSCCnegative regulation of protein phosphorylation123/4864342/187232.48e-052.82e-04123
GO:005134829SkincSCCnegative regulation of transferase activity100/4864268/187232.60e-052.94e-04100
GO:0034614111SkincSCCcellular response to reactive oxygen species63/4864155/187234.50e-054.72e-0463
GO:003011124SkincSCCregulation of Wnt signaling pathway117/4864328/187235.80e-055.75e-04117
GO:00000795SkincSCCregulation of cyclin-dependent protein serine/threonine kinase activity41/486494/187231.53e-041.35e-0341
GO:190204123SkincSCCregulation of extrinsic apoptotic signaling pathway via death domain receptors25/486449/187231.53e-041.35e-0325
GO:190402911SkincSCCregulation of cyclin-dependent protein kinase activity42/486498/187232.05e-041.70e-0342
GO:007190024SkincSCCregulation of protein serine/threonine kinase activity123/4864359/187232.70e-042.17e-03123
GO:000862522SkincSCCextrinsic apoptotic signaling pathway via death domain receptors36/486482/187233.22e-042.57e-0336
GO:003017724SkincSCCpositive regulation of Wnt signaling pathway55/4864140/187233.72e-042.92e-0355
GO:000283122SkincSCCregulation of response to biotic stimulus112/4864327/187235.00e-043.76e-03112
GO:005067324SkincSCCepithelial cell proliferation144/4864437/187236.07e-044.38e-03144
GO:007266516SkincSCCprotein localization to vacuole30/486467/187236.60e-044.73e-0330
GO:00703019SkincSCCcellular response to hydrogen peroxide40/486498/187239.33e-046.38e-0340
GO:000275322SkincSCCcytoplasmic pattern recognition receptor signaling pathway27/486460/187231.10e-037.24e-0327
GO:003461226SkincSCCresponse to tumor necrosis factor88/4864253/187231.11e-037.31e-0388
GO:00028326SkincSCCnegative regulation of response to biotic stimulus43/4864108/187231.12e-037.36e-0343
GO:003320915SkincSCCtumor necrosis factor-mediated signaling pathway39/486499/187232.33e-031.36e-0239
GO:0006469110SkincSCCnegative regulation of protein kinase activity74/4864212/187232.36e-031.37e-0274
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa0516920CervixCCEpstein-Barr virus infection57/1267202/84657.30e-077.39e-064.37e-0657
hsa0465718CervixCCIL-17 signaling pathway31/126794/84658.71e-067.43e-054.39e-0531
hsa046686CervixCCTNF signaling pathway28/1267114/84654.60e-031.62e-029.59e-0328
hsa046213CervixCCNOD-like receptor signaling pathway41/1267186/84655.90e-031.95e-021.15e-0241
hsa05169110CervixCCEpstein-Barr virus infection57/1267202/84657.30e-077.39e-064.37e-0657
hsa0465719CervixCCIL-17 signaling pathway31/126794/84658.71e-067.43e-054.39e-0531
hsa0466813CervixCCTNF signaling pathway28/1267114/84654.60e-031.62e-029.59e-0328
hsa0462112CervixCCNOD-like receptor signaling pathway41/1267186/84655.90e-031.95e-021.15e-0241
hsa0465722CervixHSIL_HPVIL-17 signaling pathway15/45994/84651.45e-041.74e-031.40e-0315
hsa0516923CervixHSIL_HPVEpstein-Barr virus infection22/459202/84651.35e-039.68e-037.82e-0322
hsa0465732CervixHSIL_HPVIL-17 signaling pathway15/45994/84651.45e-041.74e-031.40e-0315
hsa0516933CervixHSIL_HPVEpstein-Barr virus infection22/459202/84651.35e-039.68e-037.82e-0322
hsa0516942CervixN_HPVEpstein-Barr virus infection19/349202/84656.54e-044.94e-033.86e-0319
hsa0516952CervixN_HPVEpstein-Barr virus infection19/349202/84656.54e-044.94e-033.86e-0319
hsa0516924EndometriumAEHEpstein-Barr virus infection42/1197202/84655.72e-033.05e-022.23e-0242
hsa05169111EndometriumAEHEpstein-Barr virus infection42/1197202/84655.72e-033.05e-022.23e-0242
hsa0516925EndometriumEECEpstein-Barr virus infection47/1237202/84656.17e-044.41e-033.29e-0347
hsa046687EndometriumEECTNF signaling pathway27/1237114/84656.47e-033.22e-022.40e-0227
hsa0465720EndometriumEECIL-17 signaling pathway23/123794/84657.61e-033.63e-022.71e-0223
hsa0516934EndometriumEECEpstein-Barr virus infection47/1237202/84656.17e-044.41e-033.29e-0347
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Cell-cell communication analysis

check buttonIdentification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states
LigandReceptorLRpairPathwayTissueDisease Stage
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Single-cell gene regulatory network inference analysis

check buttonFind out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states
TFCell TypeTissueDisease StageTarget GeneRSSRegulon Activity
∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.
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Somatic mutation of malignant transformation related genes

check buttonAnnotation of somatic variants for genes involved in malignant transformation
Hugo SymbolVariant ClassVariant ClassificationdbSNP RSHGVScHGVSpHGVSp ShortSWISSPROTBIOTYPESIFTPolyPhenTumor Sample BarcodeTissueHistologySexAgeStageTherapy TypesDrugsOutcome
TNFAIP3SNVMissense_Mutationc.36N>Cp.Leu12Phep.L12FP21580protein_codingtolerated(0.29)benign(0.2)TCGA-5L-AAT1-01Breastbreast invasive carcinomaFemale<65III/IVHormone TherapyletrozolSD
TNFAIP3SNVMissense_Mutationc.1439N>Ap.Ser480Asnp.S480NP21580protein_codingdeleterious(0.01)benign(0.003)TCGA-A2-A04P-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapytaxolPD
TNFAIP3SNVMissense_Mutationc.979N>Tp.Ala327Serp.A327SP21580protein_codingtolerated(0.07)benign(0.305)TCGA-A2-A0YG-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapycytoxanSD
TNFAIP3SNVMissense_Mutationc.650N>Cp.Ser217Thrp.S217TP21580protein_codingdeleterious(0.01)possibly_damaging(0.79)TCGA-AO-A1KR-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapycyclophosphamideSD
TNFAIP3SNVMissense_Mutationc.1711N>Ap.Val571Ilep.V571IP21580protein_codingtolerated(0.48)benign(0)TCGA-BH-A0H6-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
TNFAIP3deletionFrame_Shift_Delnovelc.285_294delNNNNNNNNNNp.Lys96ValfsTer24p.K96Vfs*24P21580protein_codingTCGA-A2-A25B-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapytaxoterePD
TNFAIP3insertionFrame_Shift_Insnovelc.2184_2185insACATTAGTp.Ser729ThrfsTer90p.S729Tfs*90P21580protein_codingTCGA-AR-A0TW-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapydoxorubicinPD
TNFAIP3SNVMissense_Mutationrs775850329c.259N>Gp.Arg87Glyp.R87GP21580protein_codingdeleterious(0.03)benign(0.009)TCGA-C5-A2M2-01Cervixcervical & endocervical cancerFemale<65I/IIUnknownUnknownSD
TNFAIP3SNVMissense_Mutationc.2193N>Tp.Glu731Aspp.E731DP21580protein_codingtolerated(0.67)benign(0.031)TCGA-DS-A7WF-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycisplatinPD
TNFAIP3SNVMissense_Mutationnovelc.217N>Gp.Ile73Valp.I73VP21580protein_codingtolerated(1)benign(0)TCGA-5M-AAT4-01Colorectumcolon adenocarcinomaMale>=65III/IVUnknownUnknownPD
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Related drugs of malignant transformation related genes

check buttonIdentification of chemicals and drugs interact with genes involved in malignant transfromation
(DGIdb 4.0)
Entrez IDSymbolCategoryInteraction TypesDrug Claim NameDrug NamePMIDs
7128TNFAIP3PROTEASE, ENZYME, CLINICALLY ACTIONABLE, KINASETumor necrosis factor alpha (TNF-alpha) inhibitors24776844,30653751
7128TNFAIP3PROTEASE, ENZYME, CLINICALLY ACTIONABLE, KINASEustekinumabUSTEKINUMAB27564082,23521149
7128TNFAIP3PROTEASE, ENZYME, CLINICALLY ACTIONABLE, KINASEmethotrexateMETHOTREXATE20921970
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