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: GADD45A

Gene summary for GADD45A

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

GADD45A

Gene ID

1647

Gene namegrowth arrest and DNA damage inducible alpha
Gene AliasDDIT1
Cytomap1p31.3
Gene Typeprotein-coding
GO ID

GO:0000079

UniProtAcc

P24522


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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
1647GADD45AGSM4909282HumanBreastIDC3.67e-104.90e-01-0.0288
1647GADD45AGSM4909285HumanBreastIDC1.76e-02-1.98e-010.21
1647GADD45AGSM4909286HumanBreastIDC1.19e-03-3.80e-010.1081
1647GADD45AGSM4909290HumanBreastIDC1.87e-04-3.93e-010.2096
1647GADD45AGSM4909291HumanBreastIDC1.00e-02-4.08e-010.1753
1647GADD45AGSM4909293HumanBreastIDC5.29e-09-4.44e-010.1581
1647GADD45AGSM4909294HumanBreastIDC1.35e-05-4.21e-010.2022
1647GADD45AGSM4909296HumanBreastIDC6.75e-05-4.10e-010.1524
1647GADD45AGSM4909298HumanBreastIDC1.17e-05-4.59e-010.1551
1647GADD45AGSM4909301HumanBreastIDC5.73e-08-4.68e-010.1577
1647GADD45AGSM4909302HumanBreastIDC4.22e-04-3.75e-010.1545
1647GADD45AGSM4909304HumanBreastIDC9.07e-03-4.02e-010.1636
1647GADD45AGSM4909306HumanBreastIDC3.65e-03-3.75e-010.1564
1647GADD45AGSM4909307HumanBreastIDC1.96e-02-4.03e-010.1569
1647GADD45AGSM4909308HumanBreastIDC3.96e-06-3.81e-010.158
1647GADD45AGSM4909309HumanBreastIDC1.22e-02-3.47e-010.0483
1647GADD45AGSM4909311HumanBreastIDC6.23e-16-5.32e-010.1534
1647GADD45AGSM4909312HumanBreastIDC3.72e-14-5.04e-010.1552
1647GADD45AGSM4909317HumanBreastIDC1.04e-03-3.77e-010.1355
1647GADD45AGSM4909319HumanBreastIDC1.41e-16-5.23e-010.1563
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
BreastThe 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.IDC: Invasive ductal carcinoma
DCIS: Ductal carcinoma in situ
Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
LungThe 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.AAH: Atypical adenomatous hyperplasia
AIS: Adenocarcinoma in situ
IAC: Invasive lung adenocarcinoma
MIA: Minimally invasive adenocarcinoma
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:007126016ThyroidPTCcellular response to mechanical stimulus44/596881/187232.34e-052.33e-0444
GO:0010631111ThyroidPTCepithelial cell migration149/5968357/187234.83e-054.33e-04149
GO:0090132111ThyroidPTCepithelium migration149/5968360/187237.89e-056.74e-04149
GO:0090130111ThyroidPTCtissue migration150/5968365/187231.13e-049.01e-04150
GO:0010632111ThyroidPTCregulation of epithelial cell migration123/5968292/187231.33e-041.05e-03123
GO:190402912ThyroidPTCregulation of cyclin-dependent protein kinase activity49/596898/187231.40e-041.09e-0349
GO:000007912ThyroidPTCregulation of cyclin-dependent protein serine/threonine kinase activity47/596894/187231.90e-041.42e-0347
GO:2000377110ThyroidPTCregulation of reactive oxygen species metabolic process71/5968157/187233.03e-042.12e-0371
GO:00310235ThyroidPTCmicrotubule organizing center organization65/5968143/187234.48e-042.96e-0365
GO:00070984ThyroidPTCcentrosome cycle59/5968130/187238.39e-045.16e-0359
GO:000725419ThyroidPTCJNK cascade73/5968167/187238.41e-045.17e-0373
GO:007190112ThyroidPTCnegative regulation of protein serine/threonine kinase activity55/5968120/187239.30e-045.65e-0355
GO:0070302110ThyroidPTCregulation of stress-activated protein kinase signaling cascade83/5968195/187231.04e-036.21e-0383
GO:0032872110ThyroidPTCregulation of stress-activated MAPK cascade81/5968192/187231.62e-038.95e-0381
GO:2000379110ThyroidPTCpositive regulation of reactive oxygen species metabolic process37/596876/187231.64e-039.02e-0337
GO:004354219ThyroidPTCendothelial cell migration112/5968279/187232.03e-031.09e-02112
GO:00331356ThyroidPTCregulation of peptidyl-serine phosphorylation62/5968144/187233.05e-031.50e-0262
GO:001059416ThyroidPTCregulation of endothelial cell migration91/5968232/187231.03e-024.18e-0291
GO:001056334ThyroidATCnegative regulation of phosphorus metabolic process234/6293442/187232.30e-172.31e-15234
GO:004593634ThyroidATCnegative regulation of phosphate metabolic process233/6293441/187233.68e-173.47e-15233
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa0516922BreastIDCEpstein-Barr virus infection45/867202/84653.16e-076.05e-064.52e-0645
hsa0421824BreastIDCCellular senescence35/867156/84655.49e-067.43e-055.56e-0535
hsa0421022BreastIDCApoptosis31/867136/84651.34e-051.61e-041.20e-0431
hsa041157BreastIDCp53 signaling pathway16/86774/84652.86e-031.86e-021.39e-0216
hsa052147BreastIDCGlioma16/86775/84653.30e-032.10e-021.57e-0216
hsa052109BreastIDCColorectal cancer17/86786/84655.70e-033.13e-022.34e-0217
hsa0522010BreastIDCChronic myeloid leukemia15/86776/84659.24e-034.37e-023.27e-0215
hsa052169BreastIDCThyroid cancer9/86737/84651.06e-024.92e-023.68e-029
hsa0516932BreastIDCEpstein-Barr virus infection45/867202/84653.16e-076.05e-064.52e-0645
hsa0421834BreastIDCCellular senescence35/867156/84655.49e-067.43e-055.56e-0535
hsa0421032BreastIDCApoptosis31/867136/84651.34e-051.61e-041.20e-0431
hsa0411512BreastIDCp53 signaling pathway16/86774/84652.86e-031.86e-021.39e-0216
hsa0521413BreastIDCGlioma16/86775/84653.30e-032.10e-021.57e-0216
hsa0521014BreastIDCColorectal cancer17/86786/84655.70e-033.13e-022.34e-0217
hsa0522013BreastIDCChronic myeloid leukemia15/86776/84659.24e-034.37e-023.27e-0215
hsa0521614BreastIDCThyroid cancer9/86737/84651.06e-024.92e-023.68e-029
hsa0516941BreastDCISEpstein-Barr virus infection46/846202/84655.60e-081.13e-068.33e-0746
hsa0421844BreastDCISCellular senescence34/846156/84658.53e-061.06e-047.80e-0534
hsa0421041BreastDCISApoptosis29/846136/84655.92e-055.97e-044.40e-0429
hsa0411521BreastDCISp53 signaling pathway16/84674/84652.23e-031.47e-021.08e-0216
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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
GADD45ATREGCervixCCEIF1B,CXCL2,MZB1, etc.1.52e-01The 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.
GADD45ATREGCervixHealthyEIF1B,CXCL2,MZB1, etc.1.62e-01The 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.
GADD45ACD4TNCervixHSIL_HPVEIF1B,CXCL2,MZB1, etc.1.00e-01The 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.
GADD45ATREGCervixHSIL_HPVEIF1B,CXCL2,MZB1, etc.1.77e-01The 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.
GADD45ACD8TEXINTCervixHSIL_HPVEIF1B,CXCL2,MZB1, etc.8.50e-02The 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.
GADD45ATREGCervixN_HPVEIF1B,CXCL2,MZB1, etc.1.34e-01The 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.
∗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
GADD45ASNVMissense_Mutationrs374796115c.493N>Tp.Arg165Trpp.R165WP24522protein_codingdeleterious(0)probably_damaging(0.998)TCGA-AX-A3G8-01Endometriumuterine corpus endometrioid carcinomaFemale>=65I/IIUnknownUnknownSD
GADD45ASNVMissense_Mutationnovelc.395C>Tp.Ser132Leup.S132LP24522protein_codingtolerated(0.18)benign(0)TCGA-B5-A11E-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIUnknownUnknownSD
GADD45ASNVMissense_Mutationnovelc.448N>Gp.Ser150Glyp.S150GP24522protein_codingdeleterious(0)benign(0.328)TCGA-D1-A2G0-01Endometriumuterine corpus endometrioid carcinomaFemale>=65I/IIUnknownUnknownSD
GADD45ASNVMissense_Mutationnovelc.63N>Ap.Asp21Glup.D21EP24522protein_codingtolerated(0.52)benign(0)TCGA-DI-A1BU-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIChemotherapypaclitaxelSD
GADD45ASNVMissense_Mutationnovelc.53N>Cp.Lys18Thrp.K18TP24522protein_codingtolerated(0.93)benign(0)TCGA-E6-A1LX-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIUnknownUnknownSD
GADD45AinsertionIn_Frame_Insnovelc.64_65insCCCTGGAGGAAGTGCTCAGCAp.Ser28_Lys29insThrLeuGluGluValLeuSerp.S28_K29insTLEEVLSP24522protein_codingTCGA-AJ-A3EM-01Endometriumuterine corpus endometrioid carcinomaFemale>=65I/IIUnknownUnknownSD
GADD45ASNVMissense_Mutationc.473C>Tp.Pro158Leup.P158LP24522protein_codingdeleterious(0)probably_damaging(1)TCGA-44-6147-01Lunglung adenocarcinomaFemale>=65I/IIUnknownUnknownSD
GADD45ASNVMissense_Mutationc.338G>Tp.Ser113Ilep.S113IP24522protein_codingtolerated(0.07)benign(0.014)TCGA-97-8547-01Lunglung adenocarcinomaFemale>=65III/IVChemotherapytaxolCR
GADD45ASNVMissense_Mutationc.344N>Tp.Gly115Valp.G115VP24522protein_codingdeleterious(0.03)benign(0.056)TCGA-66-2782-01Lunglung squamous cell carcinomaMale>=65I/IIUnspecificPD
GADD45AinsertionIn_Frame_Insnovelc.408_409insGATCCTp.Asp137_Pro138dupp.D137_P138dupP24522protein_codingTCGA-63-A5MT-01Lunglung squamous cell carcinomaMale>=65I/IIChemotherapycisplatinPD
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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
1647GADD45ADNA REPAIR, TUMOR SUPPRESSOR, KINASEDOXORUBICINDOXORUBICIN7729953
1647GADD45ADNA REPAIR, TUMOR SUPPRESSOR, KINASEWORTMANNINWORTMANNIN12066222
1647GADD45ADNA REPAIR, TUMOR SUPPRESSOR, KINASECISPLATINCISPLATIN9013707,10779360
1647GADD45ADNA REPAIR, TUMOR SUPPRESSOR, KINASECHELATORS10397746
1647GADD45ADNA REPAIR, TUMOR SUPPRESSOR, KINASETROGLITAZONETROGLITAZONE15064713
1647GADD45ADNA REPAIR, TUMOR SUPPRESSOR, KINASEGENISTEINGENISTEIN15527761
1647GADD45ADNA REPAIR, TUMOR SUPPRESSOR, KINASENB101112477050
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