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: PCSK9

Gene summary for PCSK9

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

PCSK9

Gene ID

255738

Gene nameproprotein convertase subtilisin/kexin type 9
Gene AliasFH3
Cytomap1p32.3
Gene Typeprotein-coding
GO ID

GO:0001655

UniProtAcc

Q8NBP7


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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
255738PCSK9LZE2THumanEsophagusESCC4.56e-034.09e-010.082
255738PCSK9LZE7THumanEsophagusESCC8.65e-032.60e-010.0667
255738PCSK9P2T-EHumanEsophagusESCC5.04e-092.35e-010.1177
255738PCSK9P4T-EHumanEsophagusESCC1.05e-123.33e-010.1323
255738PCSK9P10T-EHumanEsophagusESCC5.55e-245.70e-010.116
255738PCSK9P12T-EHumanEsophagusESCC2.87e-027.93e-020.1122
255738PCSK9P15T-EHumanEsophagusESCC8.92e-042.62e-010.1149
255738PCSK9P16T-EHumanEsophagusESCC8.52e-039.98e-020.1153
255738PCSK9P21T-EHumanEsophagusESCC4.18e-042.47e-010.1617
255738PCSK9P22T-EHumanEsophagusESCC5.84e-133.26e-010.1236
255738PCSK9P23T-EHumanEsophagusESCC5.65e-073.56e-010.108
255738PCSK9P26T-EHumanEsophagusESCC2.73e-143.93e-010.1276
255738PCSK9P27T-EHumanEsophagusESCC6.58e-061.94e-010.1055
255738PCSK9P28T-EHumanEsophagusESCC1.42e-133.61e-010.1149
255738PCSK9P30T-EHumanEsophagusESCC2.89e-156.04e-010.137
255738PCSK9P31T-EHumanEsophagusESCC1.59e-114.05e-010.1251
255738PCSK9P37T-EHumanEsophagusESCC5.49e-269.04e-010.1371
255738PCSK9P42T-EHumanEsophagusESCC1.22e-031.37e-010.1175
255738PCSK9P47T-EHumanEsophagusESCC1.50e-031.86e-010.1067
255738PCSK9P48T-EHumanEsophagusESCC1.29e-031.50e-010.0959
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
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
∗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:0042176111EsophagusESCCregulation of protein catabolic process280/8552391/187238.65e-262.39e-23280
GO:003238618EsophagusESCCregulation of intracellular transport243/8552337/187233.20e-237.25e-21243
GO:0009896111EsophagusESCCpositive regulation of catabolic process332/8552492/187234.36e-239.22e-21332
GO:0031331111EsophagusESCCpositive regulation of cellular catabolic process292/8552427/187238.67e-221.53e-19292
GO:1903362111EsophagusESCCregulation of cellular protein catabolic process188/8552255/187235.12e-206.62e-18188
GO:0051098111EsophagusESCCregulation of binding251/8552363/187236.73e-208.46e-18251
GO:0045732111EsophagusESCCpositive regulation of protein catabolic process167/8552231/187231.47e-161.14e-14167
GO:0071496111EsophagusESCCcellular response to external stimulus215/8552320/187234.29e-152.43e-13215
GO:000703417EsophagusESCCvacuolar transport119/8552157/187231.16e-146.30e-13119
GO:1903364111EsophagusESCCpositive regulation of cellular protein catabolic process117/8552155/187233.25e-141.66e-12117
GO:0031668111EsophagusESCCcellular response to extracellular stimulus168/8552246/187234.93e-132.23e-11168
GO:0031669110EsophagusESCCcellular response to nutrient levels148/8552215/187234.58e-121.76e-10148
GO:0048732111EsophagusESCCgland development269/8552436/187237.81e-122.95e-10269
GO:0031667111EsophagusESCCresponse to nutrient levels289/8552474/187239.25e-123.47e-10289
GO:004339320EsophagusESCCregulation of protein binding135/8552196/187233.69e-111.22e-09135
GO:005160418EsophagusESCCprotein maturation189/8552294/187237.64e-112.39e-09189
GO:0009267110EsophagusESCCcellular response to starvation110/8552156/187232.63e-107.37e-09110
GO:004259419EsophagusESCCresponse to starvation133/8552197/187234.31e-101.14e-08133
GO:00070419EsophagusESCClysosomal transport83/8552114/187233.52e-097.41e-0883
GO:0051100111EsophagusESCCnegative regulation of binding109/8552162/187232.10e-084.03e-07109
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa049794LiverHCCCholesterol metabolism41/402051/84651.33e-061.35e-057.49e-0641
hsa049795LiverHCCCholesterol metabolism41/402051/84651.33e-061.35e-057.49e-0641
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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
PCSK9deletionFrame_Shift_Delnovelc.1681+1delGQ8NBP7protein_codingTCGA-EW-A2FV-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapydocetaxelSD
PCSK9insertionNonsense_Mutationnovelc.29_30insAGp.Trp10Terp.W10*Q8NBP7protein_codingTCGA-C5-A2M1-01Cervixcervical & endocervical cancerFemale<65I/IIUnknownUnknownSD
PCSK9SNVMissense_Mutationrs376385276c.290N>Ap.Arg97Hisp.R97HQ8NBP7protein_codingdeleterious(0.03)benign(0.111)TCGA-5M-AAT6-01Colorectumcolon adenocarcinomaFemale<65III/IVUnknownUnknownPD
PCSK9SNVMissense_Mutationc.515A>Gp.Gln172Argp.Q172RQ8NBP7protein_codingtolerated(0.31)benign(0)TCGA-AA-3710-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
PCSK9SNVMissense_Mutationc.1202N>Ap.Ser401Tyrp.S401YQ8NBP7protein_codingdeleterious(0)possibly_damaging(0.882)TCGA-AA-3712-01Colorectumcolon adenocarcinomaMale>=65III/IVUnknownUnknownSD
PCSK9SNVMissense_Mutationrs145468572c.1492G>Ap.Glu498Lysp.E498KQ8NBP7protein_codingdeleterious(0.02)benign(0.432)TCGA-AA-3864-01Colorectumcolon adenocarcinomaMale>=65I/IIUnknownUnknownSD
PCSK9SNVMissense_Mutationnovelc.1187N>Ap.Ala396Glup.A396EQ8NBP7protein_codingdeleterious(0.01)possibly_damaging(0.834)TCGA-AA-3872-01Colorectumcolon adenocarcinomaMale<65III/IVUnknownUnknownSD
PCSK9SNVMissense_Mutationrs776367625c.1606N>Ap.Val536Ilep.V536IQ8NBP7protein_codingtolerated(0.77)benign(0)TCGA-AA-A02K-01Colorectumcolon adenocarcinomaMale<65III/IVChemotherapyfolinicPD
PCSK9SNVMissense_Mutationrs865914100c.940N>Ap.Ala314Thrp.A314TQ8NBP7protein_codingdeleterious(0)probably_damaging(0.989)TCGA-AY-A54L-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownPD
PCSK9SNVMissense_Mutationrs777111934c.779C>Tp.Thr260Metp.T260MQ8NBP7protein_codingdeleterious(0)probably_damaging(0.993)TCGA-G4-6322-01Colorectumcolon adenocarcinomaMale>=65III/IVChemotherapyoxaliplatinPD
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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
255738PCSK9DRUGGABLE GENOME, ENZYME, CELL SURFACE, PROTEASEBococizumabBOCOCIZUMAB
255738PCSK9DRUGGABLE GENOME, ENZYME, CELL SURFACE, PROTEASESPC5001
255738PCSK9DRUGGABLE GENOME, ENZYME, CELL SURFACE, PROTEASEinhibitor223366063BOCOCIZUMAB
255738PCSK9DRUGGABLE GENOME, ENZYME, CELL SURFACE, PROTEASEinhibitor178103355ALIROCUMAB
255738PCSK9DRUGGABLE GENOME, ENZYME, CELL SURFACE, PROTEASEinhibitorCHEMBL3137349BOCOCIZUMAB
255738PCSK9DRUGGABLE GENOME, ENZYME, CELL SURFACE, PROTEASEREGN-727ALIROCUMAB
255738PCSK9DRUGGABLE GENOME, ENZYME, CELL SURFACE, PROTEASELY3015014FROVOCIMAB
255738PCSK9DRUGGABLE GENOME, ENZYME, CELL SURFACE, PROTEASEPF-04950615BOCOCIZUMAB
255738PCSK9DRUGGABLE GENOME, ENZYME, CELL SURFACE, PROTEASEinhibitor178103915EVOLOCUMAB
255738PCSK9DRUGGABLE GENOME, ENZYME, CELL SURFACE, PROTEASEinhibitorCHEMBL2364655EVOLOCUMAB
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