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: EPHA4

Gene summary for EPHA4

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

EPHA4

Gene ID

2043

Gene nameEPH receptor A4
Gene AliasEK8
Cytomap2q36.1
Gene Typeprotein-coding
GO ID

GO:0000165

UniProtAcc

A0A024R452


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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
2043EPHA4CCI_1HumanCervixCC8.54e-105.45e-010.528
2043EPHA4CCI_3HumanCervixCC5.89e-035.91e-010.516
2043EPHA4TumorHumanCervixCC2.81e-052.79e-010.1241
2043EPHA4sample3HumanCervixCC4.30e-112.96e-010.1387
2043EPHA4T3HumanCervixCC3.59e-132.98e-010.1389
2043EPHA4HTA11_3410_2000001011HumanColorectumAD2.56e-02-2.55e-010.0155
2043EPHA4HTA11_2487_2000001011HumanColorectumSER4.24e-08-5.56e-01-0.1808
2043EPHA4HTA11_696_2000001011HumanColorectumAD6.32e-06-3.34e-01-0.1464
2043EPHA4HTA11_866_2000001011HumanColorectumAD2.83e-03-3.27e-01-0.1001
2043EPHA4HTA11_99999971662_82457HumanColorectumMSS6.22e-21-5.84e-010.3859
2043EPHA4HTA11_99999973899_84307HumanColorectumMSS1.55e-06-6.21e-010.2585
2043EPHA4HTA11_99999974143_84620HumanColorectumMSS3.32e-30-6.35e-010.3005
2043EPHA4F007HumanColorectumFAP1.29e-02-3.67e-010.1176
2043EPHA4A002-C-010HumanColorectumFAP1.98e-02-1.20e-010.242
2043EPHA4A015-C-203HumanColorectumFAP1.15e-17-3.31e-01-0.1294
2043EPHA4A015-C-204HumanColorectumFAP8.55e-06-3.61e-01-0.0228
2043EPHA4A002-C-201HumanColorectumFAP7.90e-07-2.01e-010.0324
2043EPHA4A002-C-203HumanColorectumFAP6.90e-04-3.04e-010.2786
2043EPHA4A001-C-119HumanColorectumFAP1.57e-02-3.53e-01-0.1557
2043EPHA4A001-C-108HumanColorectumFAP8.90e-09-3.14e-01-0.0272
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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
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
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
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:004217610CervixCCregulation of protein catabolic process104/2311391/187239.39e-159.36e-12104
GO:005254710CervixCCregulation of peptidase activity112/2311461/187236.70e-133.08e-10112
GO:002260410CervixCCregulation of cell morphogenesis84/2311309/187231.00e-124.29e-1084
GO:004586210CervixCCpositive regulation of proteolysis95/2311372/187231.84e-126.86e-1095
GO:190336210CervixCCregulation of cellular protein catabolic process72/2311255/187235.98e-122.10e-0972
GO:005254810CervixCCregulation of endopeptidase activity103/2311432/187231.89e-115.14e-09103
GO:004578510CervixCCpositive regulation of cell adhesion101/2311437/187231.96e-103.08e-08101
GO:190305010CervixCCregulation of proteolysis involved in cellular protein catabolic process60/2311221/187231.82e-091.98e-0760
GO:001095210CervixCCpositive regulation of peptidase activity54/2311197/187238.06e-096.99e-0754
GO:003367410CervixCCpositive regulation of kinase activity101/2311467/187238.66e-097.22e-07101
GO:004586110CervixCCnegative regulation of proteolysis80/2311351/187232.88e-081.98e-0680
GO:00452169CervixCCcell-cell junction organization53/2311200/187233.83e-082.53e-0653
GO:00430877CervixCCregulation of GTPase activity79/2311348/187234.21e-082.60e-0679
GO:00458608CervixCCpositive regulation of protein kinase activity85/2311386/187235.61e-083.29e-0685
GO:003133010CervixCCnegative regulation of cellular catabolic process63/2311262/187231.10e-075.68e-0663
GO:001095010CervixCCpositive regulation of endopeptidase activity48/2311179/187231.12e-075.71e-0648
GO:005109810CervixCCregulation of binding80/2311363/187231.32e-076.42e-0680
GO:00107699CervixCCregulation of cell morphogenesis involved in differentiation31/231196/187232.43e-071.05e-0531
GO:00163587CervixCCdendrite development58/2311243/187234.52e-071.76e-0558
GO:19030349CervixCCregulation of response to wounding44/2311167/187236.33e-072.31e-0544
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa043609CervixCCAxon guidance47/1267182/84658.13e-055.38e-043.18e-0447
hsa0436012CervixCCAxon guidance47/1267182/84658.13e-055.38e-043.18e-0447
hsa04360ColorectumADAxon guidance61/2092182/84654.36e-032.17e-021.38e-0261
hsa043601ColorectumADAxon guidance61/2092182/84654.36e-032.17e-021.38e-0261
hsa043602ColorectumMSSAxon guidance54/1875182/84651.03e-023.69e-022.26e-0254
hsa043603ColorectumMSSAxon guidance54/1875182/84651.03e-023.69e-022.26e-0254
hsa043604ColorectumFAPAxon guidance47/1404182/84659.09e-045.20e-033.16e-0347
hsa043605ColorectumFAPAxon guidance47/1404182/84659.09e-045.20e-033.16e-0347
hsa043606ColorectumCRCAxon guidance43/1091182/84654.38e-058.70e-045.90e-0443
hsa043607ColorectumCRCAxon guidance43/1091182/84654.38e-058.70e-045.90e-0443
hsa0436016EsophagusESCCAxon guidance108/4205182/84655.13e-031.30e-026.67e-03108
hsa0436017EsophagusESCCAxon guidance108/4205182/84655.13e-031.30e-026.67e-03108
hsa043608LungIACAxon guidance34/1053182/84659.31e-033.62e-022.41e-0234
hsa0436011LungIACAxon guidance34/1053182/84659.31e-033.62e-022.41e-0234
hsa0436021LungAISAxon guidance34/961182/84652.22e-031.37e-028.80e-0334
hsa0436031LungAISAxon guidance34/961182/84652.22e-031.37e-028.80e-0334
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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
EFNA1EPHA4EFNA1_EPHA4EPHACervixCC
EFNA5EPHA4EFNA5_EPHA4EPHACervixCC
EFNB1EPHA4EFNB1_EPHA4EPHBCervixCC
EFNB2EPHA4EFNB2_EPHA4EPHBCervixCC
EFNB1EPHA4EFNB1_EPHA4EPHBCRCAD
EFNB2EPHA4EFNB2_EPHA4EPHBCRCAD
EFNA1EPHA4EFNA1_EPHA4EPHACRCAD
EFNA5EPHA4EFNA5_EPHA4EPHACRCAD
EFNA1EPHA4EFNA1_EPHA4EPHACRCADJ
EFNA5EPHA4EFNA5_EPHA4EPHACRCADJ
EFNB1EPHA4EFNB1_EPHA4EPHBCRCADJ
EFNB2EPHA4EFNB2_EPHA4EPHBCRCADJ
EFNA1EPHA4EFNA1_EPHA4EPHACRCFAP
EFNA5EPHA4EFNA5_EPHA4EPHACRCFAP
EFNB2EPHA4EFNB2_EPHA4EPHBCRCFAP
EFNA1EPHA4EFNA1_EPHA4EPHACRCHealthy
EFNA5EPHA4EFNA5_EPHA4EPHACRCHealthy
EFNB2EPHA4EFNB2_EPHA4EPHBCRCHealthy
EFNA1EPHA4EFNA1_EPHA4EPHACRCMSI-H
EFNA3EPHA4EFNA3_EPHA4EPHACRCMSI-H
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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
EPHA4SNVMissense_Mutationnovelc.2934G>Cp.Gln978Hisp.Q978HP54764protein_codingtolerated(0.45)benign(0)TCGA-5L-AAT1-01Breastbreast invasive carcinomaFemale<65III/IVHormone TherapyletrozolSD
EPHA4SNVMissense_Mutationrs376275374c.2182C>Tp.Arg728Cysp.R728CP54764protein_codingdeleterious(0.01)probably_damaging(0.99)TCGA-A1-A0SI-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownSD
EPHA4SNVMissense_Mutationc.896N>Gp.Ser299Cysp.S299CP54764protein_codingdeleterious(0)possibly_damaging(0.606)TCGA-A8-A094-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
EPHA4SNVMissense_Mutationrs140023331c.2918N>Ap.Arg973Glnp.R973QP54764protein_codingtolerated(0.1)benign(0.01)TCGA-AN-A046-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
EPHA4SNVMissense_Mutationnovelc.1474N>Tp.Arg492Trpp.R492WP54764protein_codingdeleterious(0)probably_damaging(0.926)TCGA-AN-A046-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
EPHA4SNVMissense_Mutationc.701T>Cp.Val234Alap.V234AP54764protein_codingdeleterious(0)probably_damaging(0.996)TCGA-BH-A18G-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
EPHA4insertionNonsense_Mutationnovelc.574_575insAATGAAATTAATCTTGATGAAAGACCTCTTTATTTCTCp.Ile192LysfsTer2p.I192Kfs*2P54764protein_codingTCGA-A8-A09B-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapy5-fluorouracilSD
EPHA4insertionFrame_Shift_Insnovelc.210_211insTGGGGCTTAGTGCGAGTAATp.Gln71TrpfsTer12p.Q71Wfs*12P54764protein_codingTCGA-AN-A03X-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
EPHA4insertionIn_Frame_Insnovelc.208_209insCCATATTGCAGTTTTTTCp.Tyr70delinsSerIleLeuGlnPhePheHisp.Y70delinsSILQFFHP54764protein_codingTCGA-AN-A03X-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
EPHA4SNVMissense_Mutationc.1900N>Ap.Glu634Lysp.E634KP54764protein_codingdeleterious(0)probably_damaging(0.999)TCGA-C5-A1BK-01Cervixcervical & endocervical cancerFemale<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
2043EPHA4DRUGGABLE GENOME, KINASE, CELL SURFACE, TYROSINE KINASEinhibitorCHEMBL24828VANDETANIB
2043EPHA4DRUGGABLE GENOME, KINASE, CELL SURFACE, TYROSINE KINASEinhibitor249565821
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