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: FOXO3

Gene summary for FOXO3

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

FOXO3

Gene ID

2309

Gene nameforkhead box O3
Gene AliasAF6q21
Cytomap6q21
Gene Typeprotein-coding
GO ID

GO:0000003

UniProtAcc

O43524


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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
2309FOXO3HTA11_411_2000001011HumanColorectumSER1.80e-059.34e-01-0.2602
2309FOXO3HTA11_2112_2000001011HumanColorectumSER5.40e-036.94e-01-0.2196
2309FOXO3HTA11_866_3004761011HumanColorectumAD7.41e-044.19e-010.096
2309FOXO3HTA11_6818_2000001021HumanColorectumAD3.33e-035.23e-010.0588
2309FOXO3HTA11_99999965062_69753HumanColorectumMSI-H1.08e-071.02e+000.3487
2309FOXO3HTA11_99999965104_69814HumanColorectumMSS1.36e-151.39e+000.281
2309FOXO3HTA11_99999971662_82457HumanColorectumMSS1.45e-046.84e-010.3859
2309FOXO3HTA11_99999973899_84307HumanColorectumMSS9.73e-036.51e-010.2585
2309FOXO3A015-C-203HumanColorectumFAP2.14e-18-3.99e-01-0.1294
2309FOXO3A015-C-204HumanColorectumFAP1.07e-02-2.31e-01-0.0228
2309FOXO3A002-C-201HumanColorectumFAP2.95e-10-3.14e-010.0324
2309FOXO3A001-C-119HumanColorectumFAP2.31e-03-4.22e-01-0.1557
2309FOXO3A001-C-108HumanColorectumFAP3.74e-12-3.41e-01-0.0272
2309FOXO3A002-C-205HumanColorectumFAP1.11e-21-5.67e-01-0.1236
2309FOXO3A015-C-006HumanColorectumFAP4.24e-13-5.63e-01-0.0994
2309FOXO3A015-C-106HumanColorectumFAP5.24e-07-2.61e-01-0.0511
2309FOXO3A002-C-114HumanColorectumFAP6.17e-15-4.01e-01-0.1561
2309FOXO3A015-C-104HumanColorectumFAP4.55e-24-4.70e-01-0.1899
2309FOXO3A001-C-014HumanColorectumFAP1.79e-10-2.60e-010.0135
2309FOXO3A002-C-016HumanColorectumFAP2.17e-13-2.34e-010.0521
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
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:190165512ProstateTumorcellular response to ketone33/324696/187234.19e-054.76e-0433
GO:004350211ProstateTumorregulation of muscle adaptation33/324698/187236.69e-057.18e-0433
GO:007030114ProstateTumorcellular response to hydrogen peroxide33/324698/187236.69e-057.18e-0433
GO:199008914ProstateTumorresponse to nerve growth factor22/324656/187238.33e-058.38e-0422
GO:003647318ProstateTumorcell death in response to oxidative stress32/324695/187238.50e-058.48e-0432
GO:001050814ProstateTumorpositive regulation of autophagy39/3246124/187238.56e-058.53e-0439
GO:009730518ProstateTumorresponse to alcohol68/3246253/187239.02e-058.88e-0468
GO:005127114ProstateTumornegative regulation of cellular component movement92/3246367/187231.03e-049.99e-0492
GO:199009013ProstateTumorcellular response to nerve growth factor stimulus21/324653/187231.04e-041.00e-0321
GO:007145614ProstateTumorcellular response to hypoxia45/3246151/187231.08e-041.03e-0345
GO:190040717ProstateTumorregulation of cellular response to oxidative stress30/324689/187231.38e-041.27e-0330
GO:000840612ProstateTumorgonad development60/3246221/187231.68e-041.50e-0360
GO:004277012ProstateTumorsignal transduction in response to DNA damage49/3246172/187231.87e-041.65e-0349
GO:200014614ProstateTumornegative regulation of cell motility89/3246359/187231.99e-041.74e-0389
GO:000941017ProstateTumorresponse to xenobiotic stimulus110/3246462/187232.13e-041.84e-03110
GO:009025713ProstateTumorregulation of muscle system process66/3246252/187232.54e-042.13e-0366
GO:000754811ProstateTumorsex differentiation71/3246276/187232.70e-042.24e-0371
GO:003428419ProstateTumorresponse to monosaccharide60/3246225/187232.84e-042.31e-0360
GO:003461217ProstateTumorresponse to tumor necrosis factor66/3246253/187232.87e-042.32e-0366
GO:007259315ProstateTumorreactive oxygen species metabolic process63/3246239/187232.87e-042.32e-0363
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa05213ColorectumADEndometrial cancer29/209258/84652.69e-052.57e-041.64e-0429
hsa04218ColorectumADCellular senescence53/2092156/84655.55e-032.48e-021.58e-0253
hsa052131ColorectumADEndometrial cancer29/209258/84652.69e-052.57e-041.64e-0429
hsa042181ColorectumADCellular senescence53/2092156/84655.55e-032.48e-021.58e-0253
hsa052082ColorectumSERChemical carcinogenesis - reactive oxygen species103/1580223/84651.60e-217.57e-205.50e-20103
hsa051312ColorectumSERShigellosis87/1580247/84653.07e-107.27e-095.28e-0987
hsa047222ColorectumSERNeurotrophin signaling pathway35/1580119/84652.80e-032.02e-021.47e-0235
hsa052132ColorectumSEREndometrial cancer20/158058/84653.05e-032.11e-021.53e-0220
hsa042132ColorectumSERLongevity regulating pathway - multiple species20/158062/84657.15e-033.77e-022.74e-0220
hsa041372ColorectumSERMitophagy - animal22/158072/84659.93e-034.78e-023.47e-0222
hsa052083ColorectumSERChemical carcinogenesis - reactive oxygen species103/1580223/84651.60e-217.57e-205.50e-20103
hsa051313ColorectumSERShigellosis87/1580247/84653.07e-107.27e-095.28e-0987
hsa047223ColorectumSERNeurotrophin signaling pathway35/1580119/84652.80e-032.02e-021.47e-0235
hsa052133ColorectumSEREndometrial cancer20/158058/84653.05e-032.11e-021.53e-0220
hsa042133ColorectumSERLongevity regulating pathway - multiple species20/158062/84657.15e-033.77e-022.74e-0220
hsa041373ColorectumSERMitophagy - animal22/158072/84659.93e-034.78e-023.47e-0222
hsa052084ColorectumMSSChemical carcinogenesis - reactive oxygen species118/1875223/84652.71e-244.54e-222.78e-22118
hsa051314ColorectumMSSShigellosis94/1875247/84656.82e-091.34e-078.23e-0894
hsa052134ColorectumMSSEndometrial cancer27/187558/84653.18e-053.23e-041.98e-0427
hsa047224ColorectumMSSNeurotrophin signaling pathway45/1875119/84657.04e-056.55e-044.02e-0445
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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
FOXO3MYOEPIBreastHealthyTES,SLC38A1,ARID5B, etc.4.39e-01The 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.
FOXO3INMONBreastHealthyTHBS1,ACSL1,CYP1B1, etc.1.71e-01The 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.
FOXO3MONBreastHealthyTHBS1,ACSL1,CYP1B1, etc.1.00e-01The 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.
FOXO3INMONBreastPrecancerTHBS1,ACSL1,CYP1B1, etc.2.93e-01The 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.
FOXO3CFIBColorectumADJMAPK10,XIST,FOXO1, etc.4.36e-01The 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.
FOXO3AT2LLungMIACZBTB16,ALCAM,FAM13A, etc.6.22e-01The 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.
FOXO3INMONLungAAHEREG,GLG1,PRAG1, etc.1.13e-01The 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.
FOXO3INMONProstateHealthyITSN1,UBE2R2,SLC4A7, etc.1.20e-01The 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.
∗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
FOXO3SNVMissense_Mutationnovelc.1165G>Ap.Asp389Asnp.D389NO43524protein_codingtolerated(0.2)possibly_damaging(0.644)TCGA-AN-A046-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
FOXO3SNVMissense_Mutationnovelc.1327N>Ap.Leu443Ilep.L443IO43524protein_codingdeleterious(0.01)possibly_damaging(0.637)TCGA-AQ-A04J-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapycytoxanSD
FOXO3SNVMissense_Mutationnovelc.1873N>Cp.Glu625Glnp.E625QO43524protein_codingdeleterious(0.01)possibly_damaging(0.616)TCGA-AR-A0TT-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapydoxorubicinSD
FOXO3insertionFrame_Shift_Insnovelc.1325_1326insTGGTTp.Leu443GlyfsTer45p.L443Gfs*45O43524protein_codingTCGA-AQ-A04J-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapycytoxanSD
FOXO3SNVMissense_Mutationnovelc.907C>Ap.Leu303Metp.L303MO43524protein_codingtolerated(0.05)possibly_damaging(0.898)TCGA-2W-A8YY-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycisplatinCR
FOXO3SNVMissense_Mutationnovelc.1156C>Ap.Leu386Ilep.L386IO43524protein_codingtolerated(0.18)benign(0.232)TCGA-2W-A8YY-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycisplatinCR
FOXO3SNVMissense_Mutationnovelc.730N>Ap.Gly244Argp.G244RO43524protein_codingdeleterious(0)probably_damaging(0.968)TCGA-EA-A3HS-01Cervixcervical & endocervical cancerFemale<65I/IIUnknownUnknownSD
FOXO3SNVMissense_Mutationc.1103G>Ap.Arg368Glnp.R368QO43524protein_codingdeleterious(0.02)benign(0.066)TCGA-EA-A410-01Cervixcervical & endocervical cancerFemale<65I/IIUnknownUnknownSD
FOXO3SNVMissense_Mutationc.968N>Tp.Arg323Leup.R323LO43524protein_codingdeleterious(0)possibly_damaging(0.859)TCGA-MA-AA3X-01Cervixcervical & endocervical cancerFemale<65III/IVChemotherapycisplatinCR
FOXO3SNVMissense_Mutationrs570814853c.1330C>Tp.Arg444Cysp.R444CO43524protein_codingdeleterious(0.04)benign(0.021)TCGA-AA-A02R-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownPD
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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
2309FOXO3TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLERESVERATROLRESVERATROL17513867
2309FOXO3TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLESYRINGARESINOLSYRINGARESINOL25479772
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