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: CLDN4

Gene summary for CLDN4

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

CLDN4

Gene ID

1364

Gene nameclaudin 4
Gene AliasCPE-R
Cytomap7q11.23
Gene Typeprotein-coding
GO ID

GO:0000003

UniProtAcc

O14493


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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
1364CLDN4GSM4909280HumanBreastPrecancer3.36e-043.43e-010.0305
1364CLDN4GSM4909281HumanBreastIDC1.63e-14-4.12e-010.21
1364CLDN4GSM4909282HumanBreastIDC2.01e-134.11e-01-0.0288
1364CLDN4GSM4909285HumanBreastIDC5.90e-09-2.32e-010.21
1364CLDN4GSM4909286HumanBreastIDC1.55e-23-5.52e-010.1081
1364CLDN4GSM4909288HumanBreastIDC7.42e-03-4.43e-010.0988
1364CLDN4GSM4909290HumanBreastIDC1.28e-20-7.92e-010.2096
1364CLDN4GSM4909294HumanBreastIDC2.42e-17-5.94e-010.2022
1364CLDN4GSM4909297HumanBreastIDC6.95e-14-4.57e-010.1517
1364CLDN4GSM4909298HumanBreastIDC7.84e-08-3.63e-010.1551
1364CLDN4GSM4909300HumanBreastIDC3.38e-074.00e-010.0334
1364CLDN4GSM4909302HumanBreastIDC7.19e-06-4.40e-010.1545
1364CLDN4GSM4909304HumanBreastIDC1.12e-14-4.36e-010.1636
1364CLDN4GSM4909305HumanBreastIDC7.25e-073.33e-010.0436
1364CLDN4GSM4909307HumanBreastIDC1.04e-06-4.16e-010.1569
1364CLDN4GSM4909308HumanBreastIDC2.92e-19-5.81e-010.158
1364CLDN4GSM4909311HumanBreastIDC6.44e-37-6.24e-010.1534
1364CLDN4GSM4909313HumanBreastIDC6.80e-061.84e-010.0391
1364CLDN4GSM4909315HumanBreastIDC2.60e-36-9.18e-010.21
1364CLDN4GSM4909316HumanBreastIDC2.27e-15-1.02e+000.21
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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
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:00525479BreastPrecancerregulation of peptidase activity71/1080461/187232.72e-146.94e-1271
GO:00485459BreastPrecancerresponse to steroid hormone53/1080339/187233.07e-113.66e-0953
GO:00458629BreastPrecancerpositive regulation of proteolysis51/1080372/187237.77e-095.70e-0751
GO:00109529BreastPrecancerpositive regulation of peptidase activity33/1080197/187233.01e-081.89e-0633
GO:00075653BreastPrecancerfemale pregnancy29/1080193/187232.07e-067.31e-0529
GO:00447063BreastPrecancermulti-multicellular organism process31/1080220/187233.73e-061.19e-0431
GO:00420609BreastPrecancerwound healing48/1080422/187235.48e-061.63e-0448
GO:00508789BreastPrecancerregulation of body fluid levels40/1080379/187231.68e-042.77e-0340
GO:00702933BreastPrecancerrenal absorption6/108017/187232.59e-043.83e-036
GO:19030367BreastPrecancerpositive regulation of response to wounding12/108072/187237.90e-049.30e-0312
GO:00903036BreastPrecancerpositive regulation of wound healing10/108059/187231.86e-031.81e-0210
GO:19016549BreastPrecancerresponse to ketone22/1080194/187231.89e-031.84e-0222
GO:19030348BreastPrecancerregulation of response to wounding19/1080167/187233.60e-032.98e-0219
GO:00226049BreastPrecancerregulation of cell morphogenesis29/1080309/187236.88e-034.67e-0229
GO:005254714BreastIDCregulation of peptidase activity96/1434461/187237.58e-206.15e-1796
GO:004854514BreastIDCresponse to steroid hormone70/1434339/187231.34e-144.23e-1270
GO:004586214BreastIDCpositive regulation of proteolysis66/1434372/187239.76e-111.29e-0866
GO:001095214BreastIDCpositive regulation of peptidase activity40/1434197/187231.04e-087.67e-0740
GO:000756511BreastIDCfemale pregnancy39/1434193/187231.81e-081.27e-0639
GO:00447061BreastIDCmulti-multicellular organism process41/1434220/187238.58e-085.19e-0641
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa0513018BreastPrecancerPathogenic Escherichia coli infection38/684197/84653.12e-075.81e-064.45e-0638
hsa0453018BreastPrecancerTight junction31/684169/84651.13e-051.26e-049.64e-0531
hsa0513019BreastPrecancerPathogenic Escherichia coli infection38/684197/84653.12e-075.81e-064.45e-0638
hsa0453019BreastPrecancerTight junction31/684169/84651.13e-051.26e-049.64e-0531
hsa0453024BreastIDCTight junction38/867169/84652.07e-063.20e-052.39e-0538
hsa0513024BreastIDCPathogenic Escherichia coli infection42/867197/84652.66e-063.92e-052.94e-0542
hsa0467024BreastIDCLeukocyte transendothelial migration21/867114/84655.41e-033.13e-022.34e-0221
hsa0453034BreastIDCTight junction38/867169/84652.07e-063.20e-052.39e-0538
hsa0513034BreastIDCPathogenic Escherichia coli infection42/867197/84652.66e-063.92e-052.94e-0542
hsa0467034BreastIDCLeukocyte transendothelial migration21/867114/84655.41e-033.13e-022.34e-0221
hsa0513043BreastDCISPathogenic Escherichia coli infection42/846197/84651.40e-062.15e-051.59e-0542
hsa0453044BreastDCISTight junction37/846169/84653.07e-064.20e-053.09e-0537
hsa0513053BreastDCISPathogenic Escherichia coli infection42/846197/84651.40e-062.15e-051.59e-0542
hsa0453054BreastDCISTight junction37/846169/84653.07e-064.20e-053.09e-0537
hsa0513020CervixCCPathogenic Escherichia coli infection63/1267197/84659.28e-102.00e-081.19e-0863
hsa0453020CervixCCTight junction49/1267169/84651.87e-061.78e-051.05e-0549
hsa0467020CervixCCLeukocyte transendothelial migration36/1267114/84655.22e-064.83e-052.86e-0536
hsa045147CervixCCCell adhesion molecules36/1267157/84654.94e-031.67e-029.86e-0336
hsa05130110CervixCCPathogenic Escherichia coli infection63/1267197/84659.28e-102.00e-081.19e-0863
hsa04530110CervixCCTight junction49/1267169/84651.87e-061.78e-051.05e-0549
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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
CLDN4SNVMissense_Mutationc.428N>Cp.Ile143Thrp.I143TO14493protein_codingdeleterious(0.03)benign(0.137)TCGA-BH-A18G-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
CLDN4SNVMissense_Mutationc.322C>Ap.Leu108Metp.L108MO14493protein_codingtolerated(0.12)benign(0.015)TCGA-AZ-6601-01Colorectumcolon adenocarcinomaMale>=65I/IIUnknownUnknownPD
CLDN4deletionFrame_Shift_Delc.532delNp.Leu180CysfsTer115p.L180Cfs*115O14493protein_codingTCGA-AD-A5EJ-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
CLDN4deletionFrame_Shift_Delc.532delNp.Leu180CysfsTer115p.L180Cfs*115O14493protein_codingTCGA-CK-6746-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
CLDN4SNVMissense_Mutationnovelc.259N>Gp.Ser87Glyp.S87GO14493protein_codingdeleterious(0.04)benign(0.026)TCGA-AP-A1DK-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIUnknownUnknownSD
CLDN4SNVMissense_Mutationnovelc.133N>Gp.Thr45Alap.T45AO14493protein_codingdeleterious(0.03)benign(0.015)TCGA-E6-A1M0-01Endometriumuterine corpus endometrioid carcinomaFemale<65III/IVChemotherapycarboplatinSD
CLDN4SNVMissense_Mutationrs782337604c.497N>Cp.Val166Alap.V166AO14493protein_codingdeleterious(0)benign(0.278)TCGA-EC-A1QX-01Endometriumuterine corpus endometrioid carcinomaFemale>=65I/IIChemotherapycyclophosphamidePD
CLDN4SNVMissense_Mutationnovelc.370N>Ap.Val124Metp.V124MO14493protein_codingtolerated(0.16)benign(0.038)TCGA-EO-A22U-01Endometriumuterine corpus endometrioid carcinomaFemale>=65I/IIUnknownUnknownSD
CLDN4SNVMissense_Mutationnovelc.327N>Tp.Glu109Aspp.E109DO14493protein_codingtolerated(0.27)benign(0.007)TCGA-EO-A22X-01Endometriumuterine corpus endometrioid carcinomaFemale<65III/IVUnspecificCarboplatinComplete Response
CLDN4SNVMissense_Mutationrs200176069c.488C>Tp.Ser163Leup.S163LO14493protein_codingdeleterious(0.03)possibly_damaging(0.686)TCGA-EY-A4KR-01Endometriumuterine corpus endometrioid carcinomaFemale<65III/IVChemotherapycarboplatinPD
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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
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