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: KLF4

Gene summary for KLF4

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

KLF4

Gene ID

9314

Gene nameKruppel like factor 4
Gene AliasEZF
Cytomap9q31.2
Gene Typeprotein-coding
GO ID

GO:0000082

UniProtAcc

O43474


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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
9314KLF4CA_HPV_3HumanCervixCC2.78e-092.73e-010.0414
9314KLF4HSIL_HPV_2HumanCervixHSIL_HPV1.73e-02-2.92e-010.0208
9314KLF4N_HPV_2HumanCervixN_HPV5.57e-112.85e-01-0.0131
9314KLF4CCII_1HumanCervixCC4.09e-02-3.41e-010.3249
9314KLF4sample3HumanCervixCC2.43e-054.69e-020.1387
9314KLF4T2HumanCervixCC4.17e-098.02e-010.0709
9314KLF4HTA11_2487_2000001011HumanColorectumSER2.28e-045.08e-01-0.1808
9314KLF4HTA11_78_2000001011HumanColorectumAD6.34e-177.28e-01-0.1088
9314KLF4HTA11_347_2000001011HumanColorectumAD3.01e-186.88e-01-0.1954
9314KLF4HTA11_411_2000001011HumanColorectumSER5.63e-061.15e+00-0.2602
9314KLF4HTA11_696_2000001011HumanColorectumAD1.49e-073.69e-01-0.1464
9314KLF4HTA11_2992_2000001011HumanColorectumSER1.51e-046.77e-01-0.1706
9314KLF4HTA11_5212_2000001011HumanColorectumAD2.05e-108.73e-01-0.2061
9314KLF4F034HumanColorectumFAP4.69e-02-1.81e-01-0.0665
9314KLF4EEC-subject1HumanEndometriumEEC4.02e-03-2.94e-01-0.2682
9314KLF4EEC-subject3HumanEndometriumEEC1.56e-05-1.36e-01-0.2525
9314KLF4GSM5276935HumanEndometriumEEC5.71e-06-3.79e-01-0.123
9314KLF4GSM5276937HumanEndometriumEEC1.08e-03-3.58e-01-0.0897
9314KLF4GSM6177620_NYU_UCEC1_lib1_lib1HumanEndometriumEEC2.46e-08-3.74e-01-0.1869
9314KLF4GSM6177620_NYU_UCEC1_lib2_lib2HumanEndometriumEEC1.27e-10-4.68e-01-0.1875
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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
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
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:006007025ThyroidATCcanonical Wnt signaling pathway154/6293303/187233.68e-101.02e-08154
GO:001097523ThyroidATCregulation of neuron projection development212/6293445/187234.16e-101.14e-08212
GO:006156423ThyroidATCaxon development220/6293467/187236.85e-101.80e-08220
GO:190198715ThyroidATCregulation of cell cycle phase transition187/6293390/187232.36e-095.61e-08187
GO:190165427ThyroidATCresponse to ketone105/6293194/187232.96e-096.96e-08105
GO:190165325ThyroidATCcellular response to peptide173/6293359/187235.87e-091.28e-07173
GO:003461433ThyroidATCcellular response to reactive oxygen species87/6293155/187236.54e-091.43e-0787
GO:0051054110ThyroidATCpositive regulation of DNA metabolic process107/6293201/187237.10e-091.54e-07107
GO:004578614ThyroidATCnegative regulation of cell cycle181/6293385/187232.64e-085.07e-07181
GO:001063131ThyroidATCepithelial cell migration169/6293357/187234.21e-087.69e-07169
GO:009013031ThyroidATCtissue migration171/6293365/187238.55e-081.47e-06171
GO:009013231ThyroidATCepithelium migration169/6293360/187238.57e-081.47e-06169
GO:000979115ThyroidATCpost-embryonic development50/629380/187231.14e-071.92e-0650
GO:200027825ThyroidATCregulation of DNA biosynthetic process62/6293106/187231.26e-072.09e-0662
GO:190199115ThyroidATCnegative regulation of mitotic cell cycle phase transition94/6293179/187231.33e-072.19e-0694
GO:007030122ThyroidATCcellular response to hydrogen peroxide58/629398/187231.81e-072.86e-0658
GO:004593015ThyroidATCnegative regulation of mitotic cell cycle117/6293235/187231.93e-073.05e-06117
GO:004484316ThyroidATCcell cycle G1/S phase transition119/6293241/187232.68e-074.10e-06119
GO:000008216ThyroidATCG1/S transition of mitotic cell cycle107/6293214/187234.83e-076.99e-06107
GO:001063231ThyroidATCregulation of epithelial cell migration137/6293292/187231.44e-061.77e-05137
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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
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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
KLF4CD8TEXPColorectumSERATF3,CHP2,MRPL55, etc.1.58e-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.
KLF4INMONEndometriumHealthyKLF2,LYZ,ATF3, etc.7.99e-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.
KLF4ECMEsophagusHealthyKLF2,ANXA1,CFD, etc.6.50e-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.
KLF4LCLungAAHTYROBP,HSP90AA1,DUSP1, etc.1.94e-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.
KLF4MDSCLungHealthyRND3,JUN,CCNL1, etc.8.74e-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.
KLF4LCLungMIACHLA-DPB1,HLA-DRB1,CD74, etc.1.59e-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.
KLF4M1MACPancreasADJSIK1,PLAUR,CXCL2, etc.1.73e-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.
KLF4PMCStomachCAGKLF2,S100P,CA2, etc.7.24e-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
KLF4SNVMissense_Mutationc.1225A>Cp.Lys409Glnp.K409QO43474protein_codingdeleterious(0)possibly_damaging(0.749)TCGA-A7-A0CG-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
KLF4SNVMissense_Mutationc.1225N>Cp.Lys409Glnp.K409QO43474protein_codingdeleterious(0)possibly_damaging(0.749)TCGA-B6-A1KI-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownSD
KLF4insertionFrame_Shift_Insnovelc.1350_1351insCCGTGTGTTTp.Thr451ProfsTer40p.T451Pfs*40O43474protein_codingTCGA-AN-A0FX-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownSD
KLF4SNVMissense_Mutationnovelc.71N>Tp.Ala24Valp.A24VO43474protein_codingtolerated(0.07)benign(0.374)TCGA-2W-A8YY-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycisplatinCR
KLF4SNVMissense_Mutationnovelc.964N>Cp.Glu322Glnp.E322QO43474protein_codingtolerated(0.11)benign(0.155)TCGA-VS-A958-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycisplatinCR
KLF4SNVMissense_Mutationrs751611404c.370N>Ap.Val124Metp.V124MO43474protein_codingtolerated(0.17)possibly_damaging(0.871)TCGA-5M-AAT6-01Colorectumcolon adenocarcinomaFemale<65III/IVUnknownUnknownPD
KLF4SNVMissense_Mutationnovelc.385T>Cp.Ser129Prop.S129PO43474protein_codingtolerated(0.14)benign(0.007)TCGA-CA-6717-01Colorectumcolon adenocarcinomaMale<65I/IIChemotherapyoxaliplatinCR
KLF4SNVMissense_Mutationc.1246N>Tp.His416Tyrp.H416YO43474protein_codingdeleterious(0)probably_damaging(0.972)TCGA-CM-6171-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
KLF4SNVMissense_Mutationc.1286N>Tp.Asp429Valp.D429VO43474protein_codingdeleterious(0)probably_damaging(0.941)TCGA-F4-6856-01Colorectumcolon adenocarcinomaMale<65I/IIAncillaryleucovorinCR
KLF4SNVMissense_Mutationc.38N>Ap.Ser13Asnp.S13NO43474protein_codingtolerated(0.11)possibly_damaging(0.723)TCGA-F4-6856-01Colorectumcolon adenocarcinomaMale<65I/IIAncillaryleucovorinCR
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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
9314KLF4TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLEAPTO-253APTO-253
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