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: DKK1

Gene summary for DKK1

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

DKK1

Gene ID

22943

Gene namedickkopf WNT signaling pathway inhibitor 1
Gene AliasDKK-1
Cytomap10q21.1
Gene Typeprotein-coding
GO ID

GO:0000122

UniProtAcc

I1W660


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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
22943DKK1LZE24THumanEsophagusESCC4.23e-04-3.35e-010.0596
22943DKK1P10T-EHumanEsophagusESCC5.34e-06-3.08e-010.116
22943DKK1P16T-EHumanEsophagusESCC1.52e-109.05e-010.1153
22943DKK1P26T-EHumanEsophagusESCC7.22e-091.20e+000.1276
22943DKK1P31T-EHumanEsophagusESCC1.88e-159.91e-010.1251
22943DKK1P40T-EHumanEsophagusESCC2.18e-021.18e+000.109
22943DKK1P62T-EHumanEsophagusESCC8.91e-131.58e+000.1302
22943DKK1P65T-EHumanEsophagusESCC7.37e-046.49e-010.0978
22943DKK1P75T-EHumanEsophagusESCC5.85e-773.21e+000.1125
22943DKK1HCC1_MengHumanLiverHCC2.16e-045.67e-020.0246
22943DKK1HCC2_MengHumanLiverHCC9.68e-047.19e-020.0107
22943DKK1HCC1HumanLiverHCC9.85e-155.25e+000.5336
22943DKK1S014HumanLiverHCC3.59e-724.31e+000.2254
22943DKK1S015HumanLiverHCC2.35e-725.11e+000.2375
22943DKK1S016HumanLiverHCC6.22e-874.91e+000.2243
22943DKK1C04HumanOral cavityOSCC1.96e-201.90e+000.2633
22943DKK1C21HumanOral cavityOSCC4.43e-572.92e+000.2678
22943DKK1C30HumanOral cavityOSCC2.19e-412.91e+000.3055
22943DKK1C07HumanOral cavityOSCC9.93e-032.11e+000.2491
22943DKK1C08HumanOral cavityOSCC2.14e-311.28e+000.1919
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
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
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
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:0022411111EsophagusESCCcellular component disassembly305/8552443/187231.94e-234.57e-21305
GO:0051098111EsophagusESCCregulation of binding251/8552363/187236.73e-208.46e-18251
GO:0043254111EsophagusESCCregulation of protein-containing complex assembly278/8552428/187233.81e-162.77e-14278
GO:0010563111EsophagusESCCnegative regulation of phosphorus metabolic process274/8552442/187232.32e-129.41e-11274
GO:0045936111EsophagusESCCnegative regulation of phosphate metabolic process273/8552441/187233.18e-121.25e-10273
GO:007190016EsophagusESCCregulation of protein serine/threonine kinase activity227/8552359/187231.12e-114.10e-10227
GO:004339320EsophagusESCCregulation of protein binding135/8552196/187233.69e-111.22e-09135
GO:0042326111EsophagusESCCnegative regulation of phosphorylation237/8552385/187231.86e-105.33e-09237
GO:001605517EsophagusESCCWnt signaling pathway268/8552444/187232.32e-106.58e-09268
GO:019873817EsophagusESCCcell-cell signaling by wnt269/8552446/187232.41e-106.79e-09269
GO:0001933111EsophagusESCCnegative regulation of protein phosphorylation213/8552342/187233.54e-109.76e-09213
GO:0051100111EsophagusESCCnegative regulation of binding109/8552162/187232.10e-084.03e-07109
GO:0070997111EsophagusESCCneuron death216/8552361/187233.49e-086.45e-07216
GO:003010018EsophagusESCCregulation of endocytosis135/8552211/187235.75e-081.02e-06135
GO:000756820EsophagusESCCaging201/8552339/187232.64e-073.94e-06201
GO:003011117EsophagusESCCregulation of Wnt signaling pathway194/8552328/187235.39e-077.14e-06194
GO:006007016EsophagusESCCcanonical Wnt signaling pathway180/8552303/187239.15e-071.17e-05180
GO:006082817EsophagusESCCregulation of canonical Wnt signaling pathway153/8552253/187231.38e-061.67e-05153
GO:00719029EsophagusESCCpositive regulation of protein serine/threonine kinase activity124/8552200/187232.27e-062.61e-05124
GO:000150317EsophagusESCCossification232/8552408/187233.00e-063.40e-05232
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa05022210EsophagusESCCPathways of neurodegeneration - multiple diseases318/4205476/84656.10e-152.04e-131.05e-13318
hsa05010210EsophagusESCCAlzheimer disease263/4205384/84651.80e-145.47e-132.80e-13263
hsa0502238EsophagusESCCPathways of neurodegeneration - multiple diseases318/4205476/84656.10e-152.04e-131.05e-13318
hsa0501038EsophagusESCCAlzheimer disease263/4205384/84651.80e-145.47e-132.80e-13263
hsa0501022LiverHCCAlzheimer disease254/4020384/84653.75e-148.97e-134.99e-13254
hsa0502222LiverHCCPathways of neurodegeneration - multiple diseases298/4020476/84656.59e-121.30e-107.22e-11298
hsa0501032LiverHCCAlzheimer disease254/4020384/84653.75e-148.97e-134.99e-13254
hsa0502232LiverHCCPathways of neurodegeneration - multiple diseases298/4020476/84656.59e-121.30e-107.22e-11298
hsa0501028Oral cavityOSCCAlzheimer disease244/3704384/84651.18e-153.60e-141.83e-14244
hsa0502228Oral cavityOSCCPathways of neurodegeneration - multiple diseases292/3704476/84651.60e-154.47e-142.28e-14292
hsa05010112Oral cavityOSCCAlzheimer disease244/3704384/84651.18e-153.60e-141.83e-14244
hsa05022112Oral cavityOSCCPathways of neurodegeneration - multiple diseases292/3704476/84651.60e-154.47e-142.28e-14292
hsa0501029Oral cavityLPAlzheimer disease197/2418384/84656.66e-223.69e-202.38e-20197
hsa0502229Oral cavityLPPathways of neurodegeneration - multiple diseases232/2418476/84657.77e-223.69e-202.38e-20232
hsa0501037Oral cavityLPAlzheimer disease197/2418384/84656.66e-223.69e-202.38e-20197
hsa0502237Oral cavityLPPathways of neurodegeneration - multiple diseases232/2418476/84657.77e-223.69e-202.38e-20232
hsa0501026ProstateBPHAlzheimer disease165/1718384/84654.03e-251.66e-231.03e-23165
hsa0502226ProstateBPHPathways of neurodegeneration - multiple diseases180/1718476/84657.70e-201.81e-181.12e-18180
hsa0431014ProstateBPHWnt signaling pathway50/1718171/84653.11e-031.15e-027.14e-0350
hsa05010111ProstateBPHAlzheimer disease165/1718384/84654.03e-251.66e-231.03e-23165
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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
DKK1SNVMissense_Mutationnovelc.424G>Ap.Asp142Asnp.D142NO94907protein_codingdeleterious(0.04)benign(0.026)TCGA-BH-A28O-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapycytoxanCR
DKK1SNVMissense_Mutationrs761830028c.187N>Ap.Ala63Thrp.A63TO94907protein_codingtolerated(0.38)benign(0.001)TCGA-A6-3809-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
DKK1SNVMissense_Mutationrs138915253c.358N>Tp.Arg120Cysp.R120CO94907protein_codingdeleterious(0)probably_damaging(0.999)TCGA-A6-5665-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownPD
DKK1SNVMissense_Mutationc.292N>Ap.Ala98Thrp.A98TO94907protein_codingtolerated(0.33)benign(0.15)TCGA-AA-3821-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
DKK1SNVMissense_Mutationrs145640971c.121G>Ap.Ala41Thrp.A41TO94907protein_codingdeleterious(0)benign(0.28)TCGA-AA-3947-01Colorectumcolon adenocarcinomaFemale<65I/IIUnknownUnknownSD
DKK1SNVMissense_Mutationc.539N>Cp.His180Prop.H180PO94907protein_codingtolerated(0.3)possibly_damaging(0.731)TCGA-AA-A03F-01Colorectumcolon adenocarcinomaFemale>=65III/IVUnknownUnknownPD
DKK1SNVMissense_Mutationrs759707601c.707N>Ap.Arg236Hisp.R236HO94907protein_codingdeleterious(0)probably_damaging(0.997)TCGA-CA-6719-01Colorectumcolon adenocarcinomaMale>=65I/IIUnknownUnknownPD
DKK1SNVMissense_Mutationnovelc.632N>Cp.Lys211Thrp.K211TO94907protein_codingdeleterious(0)probably_damaging(0.997)TCGA-AG-3892-01Colorectumrectum adenocarcinomaFemale<65I/IIUnknownUnknownSD
DKK1SNVMissense_Mutationnovelc.436N>Cp.Phe146Leup.F146LO94907protein_codingtolerated(0.5)benign(0)TCGA-A5-A0G2-01Endometriumuterine corpus endometrioid carcinomaFemale<65III/IVUnknownUnknownSD
DKK1SNVMissense_Mutationc.373G>Ap.Ala125Thrp.A125TO94907protein_codingtolerated(0.08)benign(0.044)TCGA-AP-A056-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIUnknownUnknownSD
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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
22943DKK1GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEFLUOROURACILFLUOROURACIL25788273
22943DKK1GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEPROTEASOME INHIBITOR17910634
22943DKK1GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEDHTANDROSTANOLONE17657240
22943DKK1GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEPF-04840082
22943DKK1GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEPMID27539678-Compound-8
22943DKK1GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEPMID27539678-Compound-3
22943DKK1GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEImidamide derivative 1
22943DKK1GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEOXALIPLATINOXALIPLATIN25788273
22943DKK1GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCE2-piperidine thiazole derivative 2
22943DKK1GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCE2-piperidine thiazole derivative 1
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