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: AKR1C4

Gene summary for AKR1C4

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

AKR1C4

Gene ID

1109

Gene namealdo-keto reductase family 1 member C4
Gene Alias3-alpha-HSD
Cytomap10p15.1
Gene Typeprotein-coding
GO ID

GO:0001523

UniProtAcc

P17516


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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
1109AKR1C4NAFLD1HumanLiverNAFLD1.22e-075.80e-01-0.04
1109AKR1C4S43HumanLiverCirrhotic1.16e-04-6.87e-02-0.0187
1109AKR1C4HCC1_MengHumanLiverHCC8.22e-1021.43e+000.0246
1109AKR1C4HCC2_MengHumanLiverHCC1.29e-03-1.65e-010.0107
1109AKR1C4cirrhotic2HumanLiverCirrhotic2.48e-04-1.59e-010.0201
1109AKR1C4HCC1HumanLiverHCC7.39e-054.13e+000.5336
1109AKR1C4HCC2HumanLiverHCC9.38e-395.18e+000.5341
1109AKR1C4Pt13.bHumanLiverHCC2.11e-081.51e-010.0251
1109AKR1C4Pt14.aHumanLiverHCC2.23e-043.46e-010.0169
1109AKR1C4Pt14.bHumanLiverHCC1.07e-207.41e-010.018
1109AKR1C4S014HumanLiverHCC1.86e-066.61e-010.2254
1109AKR1C4S016HumanLiverHCC2.21e-201.10e+000.2243
1109AKR1C4S027HumanLiverHCC9.64e-131.94e+000.2446
1109AKR1C4S028HumanLiverHCC3.37e-322.00e+000.2503
1109AKR1C4S029HumanLiverHCC2.40e-382.55e+000.2581
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
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
∗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:1901617LiverNAFLDorganic hydroxy compound biosynthetic process37/1882237/187234.58e-033.68e-0237
GO:00229007LiverNAFLDelectron transport chain29/1882175/187234.87e-033.84e-0229
GO:00066906LiverNAFLDicosanoid metabolic process22/1882123/187235.33e-034.11e-0222
GO:000609112LiverCirrhoticgeneration of precursor metabolites and energy238/4634490/187236.85e-311.07e-27238
GO:002290012LiverCirrhoticelectron transport chain111/4634175/187231.94e-271.52e-24111
GO:000820211LiverCirrhoticsteroid metabolic process143/4634319/187232.79e-153.18e-13143
GO:000663112LiverCirrhoticfatty acid metabolic process165/4634390/187231.29e-141.26e-12165
GO:001605312LiverCirrhoticorganic acid biosynthetic process139/4634316/187234.28e-143.83e-12139
GO:004639412LiverCirrhoticcarboxylic acid biosynthetic process137/4634314/187231.40e-131.14e-11137
GO:000606612LiverCirrhoticalcohol metabolic process141/4634353/187231.57e-108.03e-09141
GO:007233011LiverCirrhoticmonocarboxylic acid biosynthetic process93/4634214/187231.43e-096.16e-0893
GO:00066941LiverCirrhoticsteroid biosynthetic process77/4634173/187231.02e-083.91e-0777
GO:007054211LiverCirrhoticresponse to fatty acid32/463464/187231.13e-051.60e-0432
GO:004218011LiverCirrhoticcellular ketone metabolic process80/4634211/187231.40e-051.95e-0480
GO:001087611LiverCirrhoticlipid localization147/4634448/187236.24e-057.12e-04147
GO:19016572LiverCirrhoticglycosyl compound metabolic process37/463488/187232.70e-042.40e-0337
GO:00067202LiverCirrhoticisoprenoid metabolic process46/4634116/187232.71e-042.41e-0346
GO:00306384LiverCirrhoticpolyketide metabolic process8/463410/187233.84e-043.19e-038
GO:00445984LiverCirrhoticdoxorubicin metabolic process8/463410/187233.84e-043.19e-038
GO:000686911LiverCirrhoticlipid transport128/4634398/187234.54e-043.69e-03128
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa00120LiverNAFLDPrimary bile acid biosynthesis9/104317/84656.10e-051.33e-031.07e-039
hsa0520814LiverNAFLDChemical carcinogenesis - reactive oxygen species44/1043223/84659.22e-041.31e-021.06e-0244
hsa001201LiverNAFLDPrimary bile acid biosynthesis9/104317/84656.10e-051.33e-031.07e-039
hsa0520815LiverNAFLDChemical carcinogenesis - reactive oxygen species44/1043223/84659.22e-041.31e-021.06e-0244
hsa0520822LiverCirrhoticChemical carcinogenesis - reactive oxygen species121/2530223/84651.35e-144.08e-132.52e-13121
hsa0520832LiverCirrhoticChemical carcinogenesis - reactive oxygen species121/2530223/84651.35e-144.08e-132.52e-13121
hsa0520842LiverHCCChemical carcinogenesis - reactive oxygen species167/4020223/84652.85e-171.91e-151.06e-15167
hsa001202LiverHCCPrimary bile acid biosynthesis14/402017/84653.49e-031.12e-026.22e-0314
hsa0520852LiverHCCChemical carcinogenesis - reactive oxygen species167/4020223/84652.85e-171.91e-151.06e-15167
hsa001203LiverHCCPrimary bile acid biosynthesis14/402017/84653.49e-031.12e-026.22e-0314
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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
AKR1C4SNVMissense_Mutationrs201966709c.462N>Gp.Cys154Trpp.C154WP17516protein_codingdeleterious(0)probably_damaging(0.999)TCGA-A2-A0YJ-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapycytoxanPD
AKR1C4SNVMissense_Mutationrs781957701c.473G>Cp.Gly158Alap.G158AP17516protein_codingdeleterious(0.01)probably_damaging(0.99)TCGA-A8-A07R-01Breastbreast invasive carcinomaFemale>=65III/IVAncillaryzoledronicSD
AKR1C4SNVMissense_Mutationc.721N>Ap.Leu241Ilep.L241IP17516protein_codingtolerated(0.09)possibly_damaging(0.506)TCGA-AN-A046-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
AKR1C4SNVMissense_Mutationrs201966709c.462N>Gp.Cys154Trpp.C154WP17516protein_codingdeleterious(0)probably_damaging(0.999)TCGA-BH-A0C7-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapyadriamycinCR
AKR1C4SNVMissense_Mutationrs201966709c.462N>Gp.Cys154Trpp.C154WP17516protein_codingdeleterious(0)probably_damaging(0.999)TCGA-BH-A0DE-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownSD
AKR1C4SNVMissense_Mutationrs782129542c.668G>Ap.Arg223Glnp.R223QP17516protein_codingdeleterious(0.01)possibly_damaging(0.775)TCGA-BH-A1FG-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
AKR1C4SNVMissense_Mutationc.394N>Cp.Asp132Hisp.D132HP17516protein_codingdeleterious(0.01)possibly_damaging(0.519)TCGA-BH-A209-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
AKR1C4SNVMissense_Mutationc.240N>Ap.Phe80Leup.F80LP17516protein_codingdeleterious(0)probably_damaging(0.996)TCGA-FU-A3HZ-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycisplatinCR
AKR1C4SNVMissense_Mutationrs529198618c.826N>Tp.Arg276Trpp.R276WP17516protein_codingdeleterious(0.04)possibly_damaging(0.651)TCGA-AA-3984-01Colorectumcolon adenocarcinomaFemale<65I/IIUnknownUnknownSD
AKR1C4SNVMissense_Mutationrs531165422c.380N>Tp.Thr127Metp.T127MP17516protein_codingdeleterious(0)benign(0.436)TCGA-AA-A00O-01Colorectumcolon adenocarcinomaFemale>=65III/IVUnknownUnknownSD
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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
1109AKR1C4DRUGGABLE GENOME, ENZYMEdaunorubicinDAUNORUBICIN20837989
1109AKR1C4DRUGGABLE GENOME, ENZYMEexemestaneEXEMESTANE27111237
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