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: SIAH2

Gene summary for SIAH2

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

SIAH2

Gene ID

6478

Gene namesiah E3 ubiquitin protein ligase 2
Gene AliashSiah2
Cytomap3q25.1
Gene Typeprotein-coding
GO ID

GO:0006139

UniProtAcc

O43255


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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
6478SIAH2GSM4909282HumanBreastIDC7.49e-032.65e-01-0.0288
6478SIAH2GSM4909293HumanBreastIDC1.19e-245.33e-010.1581
6478SIAH2GSM4909296HumanBreastIDC1.31e-03-5.00e-020.1524
6478SIAH2GSM4909297HumanBreastIDC1.78e-08-1.32e-010.1517
6478SIAH2GSM4909298HumanBreastIDC4.10e-022.43e-010.1551
6478SIAH2GSM4909304HumanBreastIDC2.24e-639.99e-010.1636
6478SIAH2GSM4909306HumanBreastIDC2.90e-022.65e-010.1564
6478SIAH2GSM4909311HumanBreastIDC8.65e-08-1.01e-010.1534
6478SIAH2GSM4909319HumanBreastIDC1.12e-282.96e-010.1563
6478SIAH2GSM4909321HumanBreastIDC2.24e-123.14e-010.1559
6478SIAH2ctrl6HumanBreastPrecancer5.08e-044.08e-01-0.0061
6478SIAH2NCCBC14HumanBreastDCIS3.05e-04-1.36e-010.2021
6478SIAH2P1HumanBreastIDC6.38e-03-1.28e-010.1527
6478SIAH2DCIS2HumanBreastDCIS5.19e-20-2.61e-020.0085
6478SIAH2LZE4THumanEsophagusESCC8.91e-04-8.48e-020.0811
6478SIAH2LZE8THumanEsophagusESCC1.83e-02-9.24e-020.067
6478SIAH2LZE20THumanEsophagusESCC1.32e-028.51e-020.0662
6478SIAH2LZE24THumanEsophagusESCC2.07e-126.53e-010.0596
6478SIAH2LZE21THumanEsophagusESCC3.54e-076.77e-010.0655
6478SIAH2LZE6THumanEsophagusESCC7.62e-03-1.14e-010.0845
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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
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
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
∗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:004316128SkincSCCproteasome-mediated ubiquitin-dependent protein catabolic process205/4864412/187231.46e-254.16e-23205
GO:200123329SkincSCCregulation of apoptotic signaling pathway173/4864356/187232.25e-203.44e-18173
GO:190332029SkincSCCregulation of protein modification by small protein conjugation or removal125/4864242/187239.50e-181.05e-15125
GO:003139629SkincSCCregulation of protein ubiquitination107/4864210/187237.17e-155.35e-13107
GO:200123429SkincSCCnegative regulation of apoptotic signaling pathway101/4864224/187234.17e-101.70e-08101
GO:005254728SkincSCCregulation of peptidase activity177/4864461/187232.21e-098.02e-08177
GO:005254828SkincSCCregulation of endopeptidase activity165/4864432/187231.18e-083.63e-07165
GO:004328128SkincSCCregulation of cysteine-type endopeptidase activity involved in apoptotic process89/4864209/187231.20e-072.79e-0689
GO:000762323SkincSCCcircadian rhythm89/4864210/187231.55e-073.51e-0689
GO:200011628SkincSCCregulation of cysteine-type endopeptidase activity97/4864235/187232.01e-074.34e-0697
GO:200123628SkincSCCregulation of extrinsic apoptotic signaling pathway68/4864151/187233.01e-076.12e-0668
GO:009719128SkincSCCextrinsic apoptotic signaling pathway91/4864219/187233.31e-076.63e-0691
GO:001605524SkincSCCWnt signaling pathway158/4864444/187233.80e-065.70e-05158
GO:019873824SkincSCCcell-cell signaling by wnt158/4864446/187235.08e-067.38e-05158
GO:004586128SkincSCCnegative regulation of proteolysis128/4864351/187237.95e-061.09e-04128
GO:2000117111SkincSCCnegative regulation of cysteine-type endopeptidase activity41/486486/187231.20e-051.53e-0441
GO:0043154111SkincSCCnegative regulation of cysteine-type endopeptidase activity involved in apoptotic process38/486478/187231.33e-051.67e-0438
GO:004851123SkincSCCrhythmic process110/4864298/187231.83e-052.19e-04110
GO:003011124SkincSCCregulation of Wnt signaling pathway117/4864328/187235.80e-055.75e-04117
GO:005134627SkincSCCnegative regulation of hydrolase activity130/4864379/187231.74e-041.49e-03130
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
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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
SIAH2insertionNonsense_Mutationnovelc.438_439insAAGTCATATGGCCATTGATAGTTCTCATGTAATTAGTTTTGp.Leu147LysfsTer6p.L147Kfs*6O43255protein_codingTCGA-A2-A04Y-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapycytoxanSD
SIAH2insertionNonsense_Mutationnovelc.330_331insCTTTGGCCTACAGTTTGAGGCTCCTAGAAATTAp.Cys110_Cys111insLeuTrpProThrValTerGlySerTerLysLeup.C110_C111insLWPTV*GS*KLO43255protein_codingTCGA-AO-A03R-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapydoxorubicinSD
SIAH2SNVMissense_Mutationc.95N>Tp.Pro32Leup.P32LO43255protein_codingdeleterious_low_confidence(0.01)possibly_damaging(0.908)TCGA-AA-3492-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
SIAH2SNVMissense_Mutationc.876N>Ap.Met292Ilep.M292IO43255protein_codingtolerated(0.21)benign(0.009)TCGA-AA-3510-01Colorectumcolon adenocarcinomaMale>=65I/IIUnknownUnknownSD
SIAH2SNVMissense_Mutationrs765846031c.842N>Ap.Arg281Hisp.R281HO43255protein_codingdeleterious(0.04)probably_damaging(0.983)TCGA-AA-3710-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
SIAH2SNVMissense_Mutationc.745N>Ap.Val249Ilep.V249IO43255protein_codingdeleterious(0.01)possibly_damaging(0.7)TCGA-AA-3710-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
SIAH2SNVMissense_Mutationrs748812007c.883N>Ap.Asp295Asnp.D295NO43255protein_codingtolerated(0.06)probably_damaging(0.999)TCGA-AA-3877-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
SIAH2SNVMissense_Mutationc.611N>Cp.Val204Alap.V204AO43255protein_codingdeleterious(0)probably_damaging(0.928)TCGA-AA-A00N-01Colorectumcolon adenocarcinomaMale>=65I/IIUnknownUnknownPD
SIAH2SNVMissense_Mutationc.966T>Gp.Cys322Trpp.C322WO43255protein_codingdeleterious_low_confidence(0)probably_damaging(0.968)TCGA-AA-A010-01Colorectumcolon adenocarcinomaFemale<65I/IIChemotherapyfolinicCR
SIAH2SNVMissense_Mutationrs137855704c.751N>Tp.Leu251Phep.L251FO43255protein_codingdeleterious(0)possibly_damaging(0.826)TCGA-AZ-4315-01Colorectumcolon 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
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