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: RTN4

Gene summary for RTN4

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

RTN4

Gene ID

57142

Gene namereticulon 4
Gene AliasASY
Cytomap2p16.1
Gene Typeprotein-coding
GO ID

GO:0000902

UniProtAcc

Q9NQC3


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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
57142RTN4GSM4909282HumanBreastIDC8.74e-052.28e-01-0.0288
57142RTN4GSM4909286HumanBreastIDC3.74e-18-4.73e-010.1081
57142RTN4GSM4909291HumanBreastIDC2.10e-09-5.84e-010.1753
57142RTN4GSM4909294HumanBreastIDC1.64e-16-4.07e-010.2022
57142RTN4GSM4909296HumanBreastIDC1.71e-23-5.88e-010.1524
57142RTN4GSM4909297HumanBreastIDC2.30e-31-6.23e-010.1517
57142RTN4GSM4909298HumanBreastIDC2.91e-08-3.06e-010.1551
57142RTN4GSM4909301HumanBreastIDC1.58e-06-3.75e-010.1577
57142RTN4GSM4909302HumanBreastIDC3.57e-14-5.61e-010.1545
57142RTN4GSM4909308HumanBreastIDC2.13e-062.69e-010.158
57142RTN4GSM4909309HumanBreastIDC4.42e-10-5.16e-010.0483
57142RTN4GSM4909311HumanBreastIDC8.17e-58-8.40e-010.1534
57142RTN4GSM4909312HumanBreastIDC8.12e-16-3.53e-010.1552
57142RTN4GSM4909315HumanBreastIDC1.70e-03-2.17e-010.21
57142RTN4GSM4909318HumanBreastIDC1.69e-04-6.32e-010.2031
57142RTN4GSM4909319HumanBreastIDC2.26e-61-7.34e-010.1563
57142RTN4GSM4909320HumanBreastIDC1.58e-13-7.17e-010.1575
57142RTN4GSM4909321HumanBreastIDC9.94e-19-2.80e-010.1559
57142RTN4brca1HumanBreastPrecancer2.77e-113.28e-01-0.0338
57142RTN4brca2HumanBreastPrecancer1.20e-021.91e-01-0.024
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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
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:00508219BreastPrecancerprotein stabilization29/1080191/187231.67e-066.08e-0529
GO:00316479BreastPrecancerregulation of protein stability38/1080298/187233.73e-061.19e-0438
GO:00487329BreastPrecancergland development49/1080436/187236.11e-061.73e-0449
GO:00709725BreastPrecancerprotein localization to endoplasmic reticulum15/108074/187231.74e-054.17e-0415
GO:00106348BreastPrecancerpositive regulation of epithelial cell migration25/1080176/187232.75e-056.21e-0425
GO:00106319BreastPrecancerepithelial cell migration40/1080357/187234.57e-059.71e-0440
GO:00901329BreastPrecancerepithelium migration40/1080360/187235.51e-051.14e-0340
GO:00506736BreastPrecancerepithelial cell proliferation46/1080437/187236.02e-051.23e-0346
GO:00335983BreastPrecancermammary gland epithelial cell proliferation8/108026/187237.33e-051.44e-038
GO:00901309BreastPrecancertissue migration40/1080365/187237.48e-051.47e-0340
GO:00106329BreastPrecancerregulation of epithelial cell migration33/1080292/187231.74e-042.86e-0333
GO:00506786BreastPrecancerregulation of epithelial cell proliferation40/1080381/187231.88e-043.03e-0340
GO:00016678BreastPrecancerameboidal-type cell migration47/1080475/187232.19e-043.35e-0347
GO:00420633BreastPrecancergliogenesis33/1080301/187233.06e-044.40e-0333
GO:00160497BreastPrecancercell growth46/1080482/187235.63e-047.16e-0346
GO:19038299BreastPrecancerpositive regulation of cellular protein localization30/1080276/187236.48e-047.99e-0330
GO:00506793BreastPrecancerpositive regulation of epithelial cell proliferation24/1080207/187238.88e-041.02e-0224
GO:00018373BreastPrecancerepithelial to mesenchymal transition19/1080157/187231.78e-031.75e-0219
GO:00015587BreastPrecancerregulation of cell growth39/1080414/187231.81e-031.78e-0239
GO:00017017BreastPrecancerin utero embryonic development35/1080367/187232.47e-032.27e-0235
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa0501016BreastPrecancerAlzheimer disease103/684384/84651.03e-294.66e-283.57e-28103
hsa0501017BreastPrecancerAlzheimer disease103/684384/84651.03e-294.66e-283.57e-28103
hsa0501023BreastIDCAlzheimer disease107/867384/84651.70e-237.88e-225.90e-22107
hsa0501033BreastIDCAlzheimer disease107/867384/84651.70e-237.88e-225.90e-22107
hsa0501043BreastDCISAlzheimer disease105/846384/84653.23e-231.49e-211.10e-21105
hsa0501053BreastDCISAlzheimer disease105/846384/84653.23e-231.49e-211.10e-21105
hsa0501018CervixCCAlzheimer disease113/1267384/84659.67e-143.92e-122.32e-12113
hsa0501019CervixCCAlzheimer disease113/1267384/84659.67e-143.92e-122.32e-12113
hsa0501044CervixN_HPVAlzheimer disease41/349384/84651.50e-083.13e-072.45e-0741
hsa0501054CervixN_HPVAlzheimer disease41/349384/84651.50e-083.13e-072.45e-0741
hsa05010ColorectumADAlzheimer disease174/2092384/84651.82e-199.26e-185.91e-18174
hsa050101ColorectumADAlzheimer disease174/2092384/84651.82e-199.26e-185.91e-18174
hsa050104ColorectumMSSAlzheimer disease169/1875384/84651.21e-221.01e-206.21e-21169
hsa050105ColorectumMSSAlzheimer disease169/1875384/84651.21e-221.01e-206.21e-21169
hsa050108ColorectumFAPAlzheimer disease105/1404384/84653.74e-081.04e-066.33e-07105
hsa050109ColorectumFAPAlzheimer disease105/1404384/84653.74e-081.04e-066.33e-07105
hsa0501020EndometriumAEHAlzheimer disease124/1197384/84651.20e-203.91e-192.86e-19124
hsa05010110EndometriumAEHAlzheimer disease124/1197384/84651.20e-203.91e-192.86e-19124
hsa0501025EndometriumEECAlzheimer disease126/1237384/84652.25e-207.40e-195.52e-19126
hsa0501035EndometriumEECAlzheimer disease126/1237384/84652.25e-207.40e-195.52e-19126
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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
RTN4SNVMissense_Mutationc.1778C>Ap.Ala593Glup.A593EQ9NQC3protein_codingdeleterious(0.01)benign(0.273)TCGA-A1-A0SO-01Breastbreast invasive carcinomaFemale>=65I/IIChemotherapySD
RTN4SNVMissense_Mutationc.1574C>Tp.Ser525Phep.S525FQ9NQC3protein_codingdeleterious(0)benign(0.343)TCGA-AN-A041-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownSD
RTN4SNVMissense_Mutationc.3296N>Gp.Val1099Glyp.V1099GQ9NQC3protein_codingdeleterious(0)probably_damaging(0.994)TCGA-AO-A03T-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapycyclophosphamideSD
RTN4SNVMissense_Mutationc.3359N>Cp.Lys1120Thrp.K1120TQ9NQC3protein_codingdeleterious(0)probably_damaging(0.999)TCGA-AO-A128-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapydoxorubicinSD
RTN4SNVMissense_Mutationc.1960N>Ap.Glu654Lysp.E654KQ9NQC3protein_codingdeleterious(0)probably_damaging(0.985)TCGA-E2-A1IN-01Breastbreast invasive carcinomaFemale<65I/IIHormone TherapyarimidexSD
RTN4SNVMissense_Mutationc.2798N>Cp.Ser933Thrp.S933TQ9NQC3protein_codingtolerated(0.33)benign(0.015)TCGA-E9-A244-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapycyclophosphamideSD
RTN4SNVMissense_Mutationc.1261N>Cp.Asp421Hisp.D421HQ9NQC3protein_codingdeleterious(0.01)probably_damaging(0.915)TCGA-GM-A2DB-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapytaxolCR
RTN4insertionFrame_Shift_Insnovelc.3048_3049insGTATCACCAGAGGTAAGAGAGCATTGCAGATTGGGAAAACCATp.Thr1017ValfsTer53p.T1017Vfs*53Q9NQC3protein_codingTCGA-A8-A0A4-01Breastbreast invasive carcinomaFemale>=65I/IIHormone TherapytamoxiphenCR
RTN4insertionIn_Frame_Insnovelc.2685_2686insTATAAACATAATATAAAAp.Ser895_His896insTyrLysHisAsnIleLysp.S895_H896insYKHNIKQ9NQC3protein_codingTCGA-AR-A0U2-01Breastbreast invasive carcinomaFemale<65III/IVHormone TherapytamoxiphenPD
RTN4SNVMissense_Mutationnovelc.1315N>Cp.Glu439Glnp.E439QQ9NQC3protein_codingdeleterious(0)probably_damaging(0.946)TCGA-C5-A1MH-01Cervixcervical & endocervical cancerFemale>=65III/IVChemotherapycisplatinPD
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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
57142RTN4DRUGGABLE GENOMEHYPERBARIC OXYGEN12951059
57142RTN4DRUGGABLE GENOMEinhibitorCHEMBL2108679OZANEZUMAB
57142RTN4DRUGGABLE GENOMEATI-355ATINUMAB22544872
57142RTN4DRUGGABLE GENOMEANTISENSE OLIGONUCLEOTIDES14574981
57142RTN4DRUGGABLE GENOMEantibody249565934OZANEZUMAB
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