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: CCL4

Gene summary for CCL4

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

CCL4

Gene ID

6351

Gene nameC-C motif chemokine ligand 4
Gene AliasACT2
Cytomap17q12
Gene Typeprotein-coding
GO ID

GO:0000165

UniProtAcc

P13236


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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
6351CCL4GSM4909291HumanBreastIDC7.70e-063.25e-010.1753
6351CCL4GSM4909317HumanBreastIDC7.10e-042.92e-010.1355
6351CCL4GSM4909319HumanBreastIDC3.05e-041.39e-010.1563
6351CCL4NCCBC5HumanBreastDCIS2.73e-075.76e-010.2046
6351CCL4P2HumanBreastIDC1.07e-106.59e-010.21
6351CCL4CA_HPV_1HumanCervixCC1.59e-187.13e-010.0264
6351CCL4N_HPV_2HumanCervixN_HPV1.93e-359.18e-01-0.0131
6351CCL4TumorHumanCervixCC8.81e-06-1.83e-010.1241
6351CCL4T3HumanCervixCC8.81e-06-1.80e-010.1389
6351CCL4EEC-subject4HumanEndometriumEEC8.52e-238.41e-01-0.2571
6351CCL4EEC-subject5HumanEndometriumEEC4.07e-094.99e-01-0.249
6351CCL4LZE6THumanEsophagusESCC8.83e-133.09e+000.0845
6351CCL4P9T-EHumanEsophagusESCC6.31e-161.24e-010.1131
6351CCL4P10T-EHumanEsophagusESCC3.50e-02-1.67e-010.116
6351CCL4P12T-EHumanEsophagusESCC7.90e-03-1.67e-010.1122
6351CCL4P16T-EHumanEsophagusESCC3.75e-03-1.63e-010.1153
6351CCL4P22T-EHumanEsophagusESCC3.50e-02-1.67e-010.1236
6351CCL4P27T-EHumanEsophagusESCC4.74e-23-1.14e-010.1055
6351CCL4P28T-EHumanEsophagusESCC2.88e-02-5.04e-020.1149
6351CCL4P47T-EHumanEsophagusESCC7.90e-03-1.64e-010.1067
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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
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
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:001603214BreastIDCviral process75/1434415/187231.98e-124.02e-1075
GO:004440314BreastIDCbiological process involved in symbiotic interaction52/1434290/187236.55e-095.03e-0752
GO:000963613BreastIDCresponse to toxic substance44/1434262/187236.33e-073.00e-0544
GO:007162111BreastIDCgranulocyte chemotaxis26/1434125/187232.36e-069.30e-0526
GO:005090011BreastIDCleukocyte migration54/1434369/187233.10e-061.15e-0454
GO:009752911BreastIDCmyeloid leukocyte migration37/1434220/187234.65e-061.62e-0437
GO:003059511BreastIDCleukocyte chemotaxis38/1434230/187235.36e-061.76e-0438
GO:003059311BreastIDCneutrophil chemotaxis22/1434103/187238.82e-062.50e-0422
GO:006032611BreastIDCcell chemotaxis46/1434310/187231.13e-053.08e-0446
GO:009753011BreastIDCgranulocyte migration27/1434148/187231.98e-054.88e-0427
GO:199026611BreastIDCneutrophil migration23/1434122/187234.67e-051.04e-0323
GO:000268511BreastIDCregulation of leukocyte migration33/1434210/187236.10e-051.27e-0333
GO:007135613BreastIDCcellular response to tumor necrosis factor35/1434229/187236.64e-051.35e-0335
GO:001095913BreastIDCregulation of metal ion transport52/1434406/187231.76e-042.97e-0352
GO:003210311BreastIDCpositive regulation of response to external stimulus54/1434427/187231.85e-043.07e-0354
GO:003461213BreastIDCresponse to tumor necrosis factor36/1434253/187232.29e-043.64e-0336
GO:00517025BreastIDCbiological process involved in interaction with symbiont18/143494/187232.46e-043.85e-0318
GO:000716314BreastIDCestablishment or maintenance of cell polarity32/1434218/187232.84e-044.33e-0332
GO:007167711BreastIDCpositive regulation of mononuclear cell migration14/143465/187233.35e-044.98e-0314
GO:00096157BreastIDCresponse to virus47/1434367/187233.53e-045.16e-0347
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa0516324BreastIDCHuman cytomegalovirus infection39/867225/84656.66e-045.41e-034.05e-0339
hsa0516334BreastIDCHuman cytomegalovirus infection39/867225/84656.66e-045.41e-034.05e-0339
hsa0516344BreastDCISHuman cytomegalovirus infection38/846225/84658.11e-045.95e-034.38e-0338
hsa0516354BreastDCISHuman cytomegalovirus infection38/846225/84658.11e-045.95e-034.38e-0338
hsa0516318CervixCCHuman cytomegalovirus infection65/1267225/84654.59e-086.47e-073.83e-0765
hsa04062CervixCCChemokine signaling pathway43/1267192/84653.60e-031.34e-027.91e-0343
hsa0516319CervixCCHuman cytomegalovirus infection65/1267225/84654.59e-086.47e-073.83e-0765
hsa040621CervixCCChemokine signaling pathway43/1267192/84653.60e-031.34e-027.91e-0343
hsa0516325EndometriumEECHuman cytomegalovirus infection47/1237225/84656.17e-033.12e-022.33e-0247
hsa0516335EndometriumEECHuman cytomegalovirus infection47/1237225/84656.17e-033.12e-022.33e-0247
hsa05163210EsophagusESCCHuman cytomegalovirus infection148/4205225/84655.73e-074.00e-062.05e-06148
hsa040645EsophagusESCCNF-kappa B signaling pathway67/4205104/84651.62e-034.89e-032.50e-0367
hsa046234EsophagusESCCCytosolic DNA-sensing pathway49/420575/84654.35e-031.12e-025.74e-0349
hsa0516338EsophagusESCCHuman cytomegalovirus infection148/4205225/84655.73e-074.00e-062.05e-06148
hsa0406412EsophagusESCCNF-kappa B signaling pathway67/4205104/84651.62e-034.89e-032.50e-0367
hsa0462311EsophagusESCCCytosolic DNA-sensing pathway49/420575/84654.35e-031.12e-025.74e-0349
hsa0516312LiverCirrhoticHuman cytomegalovirus infection87/2530225/84652.67e-031.10e-026.76e-0387
hsa0516313LiverCirrhoticHuman cytomegalovirus infection87/2530225/84652.67e-031.10e-026.76e-0387
hsa0516322LiverHCCHuman cytomegalovirus infection131/4020225/84656.86e-042.77e-031.54e-03131
hsa0516332LiverHCCHuman cytomegalovirus infection131/4020225/84656.86e-042.77e-031.54e-03131
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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
CCL4CCR5CCL4_CCR5CCLBreastADJ
CCL4CCR5CCL4_CCR5CCLCervixADJ
CCL4CCR5CCL4_CCR5CCLCRCSER
CCL4CCR5CCL4_CCR5CCLEndometriumAEH
CCL4CCR5CCL4_CCR5CCLHNSCCADJ
CCL4ACKR2CCL4_ACKR2CCLHNSCCOSCC
CCL4ACKR2CCL4_ACKR2CCLHNSCCPrecancer
CCL4CCR5CCL4_CCR5CCLProstateADJ
CCL4CCR5CCL4_CCR5CCLProstateTumor
CCL4CCR5CCL4_CCR5CCLTHCAADJ
CCL4CCR5CCL4_CCR5CCLTHCAPrecancer
CCL4ACKR2CCL4_ACKR2CCLTHCAPrecancer
CCL4CCR5CCL4_CCR5CCLTHCAPTC
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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
CCL4SNVMissense_Mutationnovelc.191N>Gp.Val64Glyp.V64GP13236protein_codingdeleterious(0.03)probably_damaging(0.997)TCGA-AA-3713-01Colorectumcolon adenocarcinomaMale>=65III/IVChemotherapy5-fluorouracilPR
CCL4SNVMissense_Mutationrs751043350c.97G>Ap.Ala33Thrp.A33TP13236protein_codingtolerated(0.08)benign(0.202)TCGA-AZ-4313-01Colorectumcolon adenocarcinomaFemale<65I/IIUnknownUnknownSD
CCL4SNVMissense_Mutationnovelc.97N>Tp.Ala33Serp.A33SP13236protein_codingtolerated(0.62)benign(0.013)TCGA-CI-6624-01Colorectumrectum adenocarcinomaFemale<65I/IIUnknownUnknownSD
CCL4SNVMissense_Mutationrs751043350c.97N>Ap.Ala33Thrp.A33TP13236protein_codingtolerated(0.08)benign(0.202)TCGA-AX-A1CE-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIUnspecificPaclitaxelSD
CCL4SNVMissense_Mutationnovelc.230C>Ap.Pro77Hisp.P77HP13236protein_codingdeleterious(0)probably_damaging(0.999)TCGA-B5-A0JY-01Endometriumuterine corpus endometrioid carcinomaFemale<65III/IVChemotherapydoxorubicinSD
CCL4SNVMissense_Mutationnovelc.43G>Ap.Ala15Thrp.A15TP13236protein_codingtolerated(0.22)probably_damaging(0.984)TCGA-B5-A1MX-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIHormone TherapymegaceSD
CCL4SNVMissense_Mutationnovelc.101G>Tp.Cys34Phep.C34FP13236protein_codingdeleterious(0.02)probably_damaging(0.996)TCGA-D1-A163-01Endometriumuterine corpus endometrioid carcinomaFemale<65III/IVChemotherapytaxolSD
CCL4SNVMissense_Mutationnovelc.163A>Gp.Ser55Glyp.S55GP13236protein_codingdeleterious(0.02)probably_damaging(0.982)TCGA-D1-A17Q-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIUnknownUnknownSD
CCL4SNVMissense_Mutationnovelc.107N>Cp.Phe36Serp.F36SP13236protein_codingdeleterious(0)probably_damaging(0.995)TCGA-DI-A1BU-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIChemotherapypaclitaxelSD
CCL4SNVMissense_Mutationnovelc.252G>Tp.Glu84Aspp.E84DP13236protein_codingtolerated(0.11)benign(0.007)TCGA-44-6774-01Lunglung adenocarcinomaFemale<65III/IVChemotherapyalimtaSD
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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
6351CCL4DRUGGABLE GENOMEEPOEPOETIN ALFA17119331
6351CCL4DRUGGABLE GENOMECLODRONATECLODRONIC ACID12388372
6351CCL4DRUGGABLE GENOMECYCLOSPORIN A15153516
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