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: MDK

Gene summary for MDK

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

MDK

Gene ID

4192

Gene namemidkine
Gene AliasARAP
Cytomap11p11.2
Gene Typeprotein-coding
GO ID

GO:0000003

UniProtAcc

P21741


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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
4192MDKGSM4909281HumanBreastIDC4.80e-1021.26e+000.21
4192MDKGSM4909285HumanBreastIDC4.52e-538.65e-010.21
4192MDKGSM4909286HumanBreastIDC3.03e-528.61e-010.1081
4192MDKGSM4909287HumanBreastIDC1.70e-073.95e-010.2057
4192MDKGSM4909290HumanBreastIDC1.12e-176.38e-010.2096
4192MDKGSM4909291HumanBreastIDC7.59e-288.26e-010.1753
4192MDKGSM4909293HumanBreastIDC2.43e-196.29e-010.1581
4192MDKGSM4909294HumanBreastIDC1.64e-204.08e-010.2022
4192MDKGSM4909295HumanBreastIDC2.76e-054.75e-010.0898
4192MDKGSM4909296HumanBreastIDC8.04e-06-2.40e-010.1524
4192MDKGSM4909297HumanBreastIDC9.28e-135.18e-020.1517
4192MDKGSM4909299HumanBreastIDC7.24e-074.29e-010.035
4192MDKGSM4909300HumanBreastIDC9.53e-054.76e-010.0334
4192MDKGSM4909301HumanBreastIDC8.10e-10-4.06e-010.1577
4192MDKGSM4909304HumanBreastIDC1.09e-15-5.04e-010.1636
4192MDKGSM4909309HumanBreastIDC1.94e-216.05e-010.0483
4192MDKGSM4909311HumanBreastIDC3.80e-25-4.82e-010.1534
4192MDKGSM4909312HumanBreastIDC5.92e-23-5.41e-010.1552
4192MDKGSM4909313HumanBreastIDC7.38e-144.93e-010.0391
4192MDKGSM4909315HumanBreastIDC2.49e-043.66e-010.21
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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
Colorectum (GSE201348)The 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.FAP: Familial adenomatous polyposis
CRC: Colorectal cancer
Colorectum (HTA11)The 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.AD: Adenomas
SER: Sessile serrated lesions
MSI-H: Microsatellite-high colorectal cancer
MSS: Microsatellite stable colorectal cancer
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:00485459BreastPrecancerresponse to steroid hormone53/1080339/187233.07e-113.66e-0953
GO:00709979BreastPrecancerneuron death50/1080361/187237.75e-095.70e-0750
GO:00319608BreastPrecancerresponse to corticosteroid30/1080167/187232.50e-081.65e-0630
GO:00514029BreastPrecancerneuron apoptotic process38/1080246/187232.68e-081.75e-0638
GO:00975297BreastPrecancermyeloid leukocyte migration34/1080220/187231.42e-077.82e-0634
GO:00509006BreastPrecancerleukocyte migration47/1080369/187232.82e-071.39e-0547
GO:00513848BreastPrecancerresponse to glucocorticoid26/1080148/187233.32e-071.57e-0526
GO:00305956BreastPrecancerleukocyte chemotaxis34/1080230/187234.16e-071.89e-0534
GO:00457859BreastPrecancerpositive regulation of cell adhesion52/1080437/187235.74e-072.49e-0552
GO:00603266BreastPrecancercell chemotaxis41/1080310/187235.99e-072.55e-0541
GO:00716217BreastPrecancergranulocyte chemotaxis23/1080125/187236.73e-072.77e-0523
GO:19012149BreastPrecancerregulation of neuron death41/1080319/187231.27e-064.80e-0541
GO:00435237BreastPrecancerregulation of neuron apoptotic process31/1080212/187231.69e-066.08e-0531
GO:00975307BreastPrecancergranulocyte migration24/1080148/187234.04e-061.26e-0424
GO:00018196BreastPrecancerpositive regulation of cytokine production52/1080467/187234.18e-061.29e-0452
GO:00305937BreastPrecancerneutrophil chemotaxis19/1080103/187235.94e-061.71e-0419
GO:00487329BreastPrecancergland development49/1080436/187236.11e-061.73e-0449
GO:00507293BreastPrecancerpositive regulation of inflammatory response23/1080142/187236.51e-061.81e-0423
GO:0050727BreastPrecancerregulation of inflammatory response44/1080386/187231.26e-053.22e-0444
GO:00421107BreastPrecancerT cell activation52/1080487/187231.37e-053.42e-0452
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
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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
MDKSDC2MDK_SDC2MKBreastADJ
MDKSDC4MDK_SDC4MKBreastADJ
MDKITGA4_ITGB1MDK_ITGA4_ITGB1MKBreastADJ
MDKNCLMDK_NCLMKBreastADJ
MDKSDC1MDK_SDC1MKBreastDCIS
MDKSDC2MDK_SDC2MKBreastDCIS
MDKSDC4MDK_SDC4MKBreastDCIS
MDKITGA4_ITGB1MDK_ITGA4_ITGB1MKBreastDCIS
MDKITGA6_ITGB1MDK_ITGA6_ITGB1MKBreastDCIS
MDKLRP1MDK_LRP1MKBreastDCIS
MDKNCLMDK_NCLMKBreastDCIS
MDKSDC1MDK_SDC1MKBreastHealthy
MDKSDC2MDK_SDC2MKBreastHealthy
MDKSDC4MDK_SDC4MKBreastHealthy
MDKITGA4_ITGB1MDK_ITGA4_ITGB1MKBreastHealthy
MDKITGA6_ITGB1MDK_ITGA6_ITGB1MKBreastHealthy
MDKLRP1MDK_LRP1MKBreastHealthy
MDKNCLMDK_NCLMKBreastHealthy
MDKSDC1MDK_SDC1MKBreastIDC
MDKSDC2MDK_SDC2MKBreastIDC
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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
MDKSNVMissense_Mutationc.41N>Cp.Leu14Prop.L14PP21741protein_codingdeleterious(0)possibly_damaging(0.894)TCGA-B6-A0WZ-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownPD
MDKSNVMissense_Mutationrs533427797c.106G>Cp.Glu36Glnp.E36QP21741protein_codingdeleterious(0.05)benign(0.023)TCGA-C5-A1MJ-01Cervixcervical & endocervical cancerFemale<65I/IIUnknownUnknownSD
MDKSNVMissense_Mutationc.411N>Tp.Lys137Asnp.K137NP21741protein_codingtolerated(0.14)possibly_damaging(0.812)TCGA-AX-A05Z-01Endometriumuterine corpus endometrioid carcinomaFemale<65III/IVChemotherapyadriamycinSD
MDKSNVMissense_Mutationnovelc.269N>Gp.Asn90Serp.N90SP21741protein_codingtolerated(1)benign(0)TCGA-E6-A1LX-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIUnknownUnknownSD
MDKSNVMissense_Mutationnovelc.130C>Tp.Pro44Serp.P44SP21741protein_codingtolerated(0.77)benign(0.062)TCGA-FI-A2D5-01Endometriumuterine corpus endometrioid carcinomaFemale<65III/IVChemotherapycarboplatinumPD
MDKSNVMissense_Mutationnovelc.37N>Tp.Ala13Serp.A13SP21741protein_codingtolerated(0.27)benign(0.012)TCGA-91-8499-01Lunglung adenocarcinomaFemale>=65I/IIUnknownUnknownSD
MDKSNVMissense_Mutationnovelc.358N>Gp.Ile120Valp.I120VP21741protein_codingtolerated(0.72)benign(0.03)TCGA-RD-A8NB-01Stomachstomach adenocarcinomaFemale>=65III/IVUnknownUnknownPD
MDKinsertionFrame_Shift_Insnovelc.124_125insGp.Pro44AlafsTer46p.P44Afs*46P21741protein_codingTCGA-D7-A4YY-01Stomachstomach adenocarcinomaMale<65III/IVChemotherapy5-fluorouracilSD
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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
4192MDKGROWTH FACTOR, DRUGGABLE GENOME, KINASERETINOIC ACID1819274
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