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: AREG

Gene summary for AREG

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

AREG

Gene ID

374

Gene nameamphiregulin
Gene AliasAR
Cytomap4q13.3
Gene Typeprotein-coding
GO ID

GO:0000003

UniProtAcc

P15514


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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
374AREGGSM4909281HumanBreastIDC4.37e-32-9.23e-010.21
374AREGGSM4909282HumanBreastIDC3.23e-15-6.25e-01-0.0288
374AREGGSM4909285HumanBreastIDC2.25e-23-7.41e-010.21
374AREGGSM4909286HumanBreastIDC8.45e-21-5.77e-010.1081
374AREGGSM4909287HumanBreastIDC1.21e-17-7.83e-010.2057
374AREGGSM4909288HumanBreastIDC1.09e-02-7.10e-010.0988
374AREGGSM4909290HumanBreastIDC4.28e-25-9.63e-010.2096
374AREGGSM4909291HumanBreastIDC5.64e-17-9.13e-010.1753
374AREGGSM4909293HumanBreastIDC1.87e-20-7.73e-010.1581
374AREGGSM4909294HumanBreastIDC1.05e-32-9.14e-010.2022
374AREGGSM4909295HumanBreastIDC7.63e-05-6.76e-010.0898
374AREGGSM4909296HumanBreastIDC3.91e-27-8.34e-010.1524
374AREGGSM4909297HumanBreastIDC1.88e-073.19e-010.1517
374AREGGSM4909298HumanBreastIDC3.15e-20-7.28e-010.1551
374AREGGSM4909299HumanBreastIDC3.15e-06-4.39e-010.035
374AREGGSM4909301HumanBreastIDC4.83e-22-8.15e-010.1577
374AREGGSM4909302HumanBreastIDC6.65e-18-7.88e-010.1545
374AREGGSM4909304HumanBreastIDC5.32e-12-5.04e-010.1636
374AREGGSM4909305HumanBreastIDC1.49e-04-2.58e-010.0436
374AREGGSM4909306HumanBreastIDC8.55e-10-5.75e-010.1564
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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
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:00069799BreastPrecancerresponse to oxidative stress70/1080446/187231.59e-144.26e-1270
GO:00485459BreastPrecancerresponse to steroid hormone53/1080339/187233.07e-113.66e-0953
GO:00003029BreastPrecancerresponse to reactive oxygen species38/1080222/187231.47e-091.23e-0738
GO:00319608BreastPrecancerresponse to corticosteroid30/1080167/187232.50e-081.65e-0630
GO:00425429BreastPrecancerresponse to hydrogen peroxide26/1080146/187232.52e-071.26e-0526
GO:00513848BreastPrecancerresponse to glucocorticoid26/1080148/187233.32e-071.57e-0526
GO:00487329BreastPrecancergland development49/1080436/187236.11e-061.73e-0449
GO:00506736BreastPrecancerepithelial cell proliferation46/1080437/187236.02e-051.23e-0346
GO:00335983BreastPrecancermammary gland epithelial cell proliferation8/108026/187237.33e-051.44e-038
GO:00506786BreastPrecancerregulation of epithelial cell proliferation40/1080381/187231.88e-043.03e-0340
GO:00420633BreastPrecancergliogenesis33/1080301/187233.06e-044.40e-0333
GO:00016496BreastPrecancerosteoblast differentiation27/1080229/187233.35e-044.73e-0327
GO:00323555BreastPrecancerresponse to estradiol19/1080141/187234.81e-046.31e-0319
GO:00506793BreastPrecancerpositive regulation of epithelial cell proliferation24/1080207/187238.88e-041.02e-0224
GO:00515919BreastPrecancerresponse to cAMP13/108093/187232.57e-032.33e-0213
GO:0060749BreastPrecancermammary gland alveolus development5/108018/187232.88e-032.49e-025
GO:0061377BreastPrecancermammary gland lobule development5/108018/187232.88e-032.49e-025
GO:00336749BreastPrecancerpositive regulation of kinase activity42/1080467/187232.94e-032.54e-0242
GO:00466839BreastPrecancerresponse to organophosphorus16/1080131/187233.60e-032.98e-0216
GO:00605625BreastPrecancerepithelial tube morphogenesis31/1080325/187234.21e-033.31e-0231
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa0521024BreastDCISColorectal cancer16/84686/84651.03e-024.50e-023.32e-0216
hsa0521034BreastDCISColorectal cancer16/84686/84651.03e-024.50e-023.32e-0216
hsa0401210CervixCCErbB signaling pathway28/126785/84652.40e-051.82e-041.08e-0428
hsa0521010CervixCCColorectal cancer27/126786/84658.60e-055.57e-043.30e-0427
hsa043908CervixCCHippo signaling pathway40/1267157/84653.64e-041.82e-031.07e-0340
hsa040109CervixCCMAPK signaling pathway62/1267302/84654.89e-031.67e-029.86e-0362
hsa0401213CervixCCErbB signaling pathway28/126785/84652.40e-051.82e-041.08e-0428
hsa0521015CervixCCColorectal cancer27/126786/84658.60e-055.57e-043.30e-0427
hsa0439013CervixCCHippo signaling pathway40/1267157/84653.64e-041.82e-031.07e-0340
hsa0401012CervixCCMAPK signaling pathway62/1267302/84654.89e-031.67e-029.86e-0362
hsa052102ColorectumMSSColorectal cancer36/187586/84653.08e-053.22e-041.97e-0436
hsa040122ColorectumMSSErbB signaling pathway30/187585/84653.73e-031.67e-021.02e-0230
hsa04390ColorectumMSSHippo signaling pathway48/1875157/84658.32e-033.10e-021.90e-0248
hsa052103ColorectumMSSColorectal cancer36/187586/84653.08e-053.22e-041.97e-0436
hsa040123ColorectumMSSErbB signaling pathway30/187585/84653.73e-031.67e-021.02e-0230
hsa043901ColorectumMSSHippo signaling pathway48/1875157/84658.32e-033.10e-021.90e-0248
hsa052104ColorectumFAPColorectal cancer25/140486/84652.60e-031.19e-027.23e-0325
hsa04010ColorectumFAPMAPK signaling pathway68/1404302/84654.00e-031.67e-021.02e-0268
hsa04151ColorectumFAPPI3K-Akt signaling pathway75/1404354/84651.23e-024.19e-022.55e-0275
hsa052105ColorectumFAPColorectal cancer25/140486/84652.60e-031.19e-027.23e-0325
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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
AREGEGFRAREG_EGFREGFBreastADJ
AREGEGFRAREG_EGFREGFBreastDCIS
AREGEGFR_ERBB2AREG_EGFR_ERBB2EGFBreastDCIS
AREGEGFRAREG_EGFREGFBreastHealthy
AREGEGFRAREG_EGFREGFBreastPrecancer
AREGEGFRAREG_EGFREGFCervixADJ
AREGEGFRAREG_EGFREGFCervixCC
AREGEGFR_ERBB2AREG_EGFR_ERBB2EGFCervixCC
AREGEGFRAREG_EGFREGFCervixHealthy
AREGEGFRAREG_EGFREGFCervixPrecancer
AREGEGFRAREG_EGFREGFCRCADJ
AREGEGFR_ERBB2AREG_EGFR_ERBB2EGFCRCADJ
AREGEGFRAREG_EGFREGFCRCFAP
AREGEGFR_ERBB2AREG_EGFR_ERBB2EGFCRCFAP
AREGEGFRAREG_EGFREGFCRCMSI-H
AREGEGFR_ERBB2AREG_EGFR_ERBB2EGFCRCMSI-H
AREGEGFRAREG_EGFREGFEndometriumADJ
AREGEGFRAREG_EGFREGFEndometriumAEH
AREGEGFRAREG_EGFREGFEndometriumHealthy
AREGEGFRAREG_EGFREGFEsophagusADJ
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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
AREGSNVMissense_Mutationc.41N>Gp.Ser14Trpp.S14WP15514protein_codingtolerated_low_confidence(0.11)benign(0.003)TCGA-AR-A24Q-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapydoxorubicinSD
AREGSNVMissense_Mutationnovelc.474N>Tp.Glu158Aspp.E158DP15514protein_codingdeleterious(0.03)benign(0.009)TCGA-D8-A1JK-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
AREGinsertionFrame_Shift_Insrs757742243c.327_328insCp.Gln112ProfsTer7p.Q112Pfs*7P15514protein_codingTCGA-A2-A0T2-01Breastbreast invasive carcinomaFemale>=65III/IVChemotherapyxelodaPD
AREGinsertionFrame_Shift_Insrs757742243c.334dupCp.Gln112ProfsTer7p.Q112Pfs*7P15514protein_codingTCGA-AN-A0FY-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownSD
AREGinsertionNonsense_Mutationnovelc.398_399insCTAGTTGACCTTCACTATGTTTCTAATGTTTTGTATTGAATGGGp.Gly134Terp.G134*P15514protein_codingTCGA-B6-A0IN-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownPD
AREGdeletionFrame_Shift_Delc.398delAp.Asn133MetfsTer30p.N133Mfs*30P15514protein_codingTCGA-BH-A18G-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
AREGdeletionFrame_Shift_Delnovelc.290delNp.Ile97MetfsTer11p.I97Mfs*11P15514protein_codingTCGA-D8-A27V-01Breastbreast invasive carcinomaFemale<65I/IIHormone TherapytamoxiphenSD
AREGSNVMissense_Mutationnovelc.236C>Tp.Ala79Valp.A79VP15514protein_codingtolerated(0.37)benign(0.006)TCGA-2W-A8YY-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycisplatinCR
AREGSNVMissense_Mutationnovelc.405A>Cp.Lys135Asnp.K135NP15514protein_codingtolerated(0.07)probably_damaging(0.998)TCGA-CA-6718-01Colorectumcolon adenocarcinomaMale<65I/IIUnknownUnknownPD
AREGSNVMissense_Mutationnovelc.671N>Tp.Arg224Ilep.R224IP15514protein_codingdeleterious(0.04)possibly_damaging(0.829)TCGA-AG-A002-01Colorectumrectum adenocarcinomaMale<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
374AREGCELL SURFACE, GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEpanitumumabPANITUMUMAB23959273
374AREGCELL SURFACE, GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEcapecitabineCAPECITABINE25026457
374AREGCELL SURFACE, GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCECETUXIMABCETUXIMAB23374602
374AREGCELL SURFACE, GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEcetuximabCETUXIMAB23959273
374AREGCELL SURFACE, GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCECRIZOTINIBCRIZOTINIB21791641
374AREGCELL SURFACE, GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEirinotecanIRINOTECAN23959273
374AREGCELL SURFACE, GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEPANITUMUMABPANITUMUMAB26867820
374AREGCELL SURFACE, GROWTH FACTOR, DRUGGABLE GENOME, DRUG RESISTANCEradiotherapy25026457
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