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: RPS6KA4

Gene summary for RPS6KA4

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

RPS6KA4

Gene ID

8986

Gene nameribosomal protein S6 kinase A4
Gene AliasMSK2
Cytomap11q13.1
Gene Typeprotein-coding
GO ID

GO:0001816

UniProtAcc

O75676


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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
8986RPS6KA4LZE7THumanEsophagusESCC5.25e-031.71e-010.0667
8986RPS6KA4LZE22THumanEsophagusESCC2.09e-032.93e-010.068
8986RPS6KA4LZE24THumanEsophagusESCC3.23e-165.24e-010.0596
8986RPS6KA4P1T-EHumanEsophagusESCC1.65e-042.35e-010.0875
8986RPS6KA4P2T-EHumanEsophagusESCC1.20e-091.91e-010.1177
8986RPS6KA4P4T-EHumanEsophagusESCC4.47e-183.61e-010.1323
8986RPS6KA4P5T-EHumanEsophagusESCC1.53e-173.85e-010.1327
8986RPS6KA4P8T-EHumanEsophagusESCC1.45e-132.53e-010.0889
8986RPS6KA4P9T-EHumanEsophagusESCC6.14e-101.85e-010.1131
8986RPS6KA4P10T-EHumanEsophagusESCC9.86e-151.79e-010.116
8986RPS6KA4P11T-EHumanEsophagusESCC1.03e-135.65e-010.1426
8986RPS6KA4P12T-EHumanEsophagusESCC2.61e-173.88e-010.1122
8986RPS6KA4P15T-EHumanEsophagusESCC3.88e-061.38e-010.1149
8986RPS6KA4P16T-EHumanEsophagusESCC4.59e-119.64e-020.1153
8986RPS6KA4P17T-EHumanEsophagusESCC2.46e-144.79e-010.1278
8986RPS6KA4P19T-EHumanEsophagusESCC2.98e-075.55e-010.1662
8986RPS6KA4P20T-EHumanEsophagusESCC9.31e-122.37e-010.1124
8986RPS6KA4P21T-EHumanEsophagusESCC2.30e-439.35e-010.1617
8986RPS6KA4P22T-EHumanEsophagusESCC4.83e-071.39e-010.1236
8986RPS6KA4P23T-EHumanEsophagusESCC1.80e-123.01e-010.108
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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
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:001657015EsophagusESCChistone modification323/8552463/187232.61e-267.88e-24323
GO:001820514EsophagusESCCpeptidyl-lysine modification259/8552376/187233.90e-205.26e-18259
GO:001839413EsophagusESCCpeptidyl-lysine acetylation123/8552169/187236.58e-132.94e-11123
GO:004354313EsophagusESCCprotein acylation165/8552243/187231.69e-127.14e-11165
GO:000647313EsophagusESCCprotein acetylation140/8552201/187234.37e-121.69e-10140
GO:001839313EsophagusESCCinternal peptidyl-lysine acetylation114/8552158/187231.16e-114.24e-10114
GO:000647513EsophagusESCCinternal protein amino acid acetylation115/8552160/187231.43e-115.08e-10115
GO:00165735EsophagusESCChistone acetylation110/8552152/187231.95e-116.81e-10110
GO:003105614EsophagusESCCregulation of histone modification106/8552152/187231.52e-093.55e-08106
GO:00510908EsophagusESCCregulation of DNA-binding transcription factor activity252/8552440/187235.22e-076.97e-06252
GO:00310583EsophagusESCCpositive regulation of histone modification65/855292/187231.04e-061.31e-0565
GO:00182099EsophagusESCCpeptidyl-serine modification196/8552338/187233.07e-063.47e-05196
GO:001810515EsophagusESCCpeptidyl-serine phosphorylation184/8552315/187233.22e-063.61e-05184
GO:00510918EsophagusESCCpositive regulation of DNA-binding transcription factor activity155/8552260/187233.83e-064.14e-05155
GO:20007564EsophagusESCCregulation of peptidyl-lysine acetylation43/855263/187232.43e-041.50e-0343
GO:00510926EsophagusESCCpositive regulation of NF-kappaB transcription factor activity91/8552152/187232.91e-041.75e-0391
GO:19019835EsophagusESCCregulation of protein acetylation49/855277/187231.12e-035.60e-0349
GO:00350653EsophagusESCCregulation of histone acetylation36/855254/187231.49e-037.06e-0336
GO:00165721EsophagusESCChistone phosphorylation27/855239/187232.52e-031.08e-0227
GO:00331271EsophagusESCCregulation of histone phosphorylation10/855212/187238.94e-033.12e-0210
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa0466810EsophagusESCCTNF signaling pathway89/4205114/84653.36e-104.01e-092.06e-0989
hsa0466817EsophagusESCCTNF signaling pathway89/4205114/84653.36e-104.01e-092.06e-0989
hsa046689Oral cavityOSCCTNF signaling pathway82/3704114/84658.30e-109.59e-094.88e-0982
hsa0401014Oral cavityOSCCMAPK signaling pathway165/3704302/84657.11e-052.74e-041.40e-04165
hsa0466816Oral cavityOSCCTNF signaling pathway82/3704114/84658.30e-109.59e-094.88e-0982
hsa0401015Oral cavityOSCCMAPK signaling pathway165/3704302/84657.11e-052.74e-041.40e-04165
hsa0466822Oral cavityLPTNF signaling pathway49/2418114/84656.51e-043.29e-032.12e-0349
hsa0466832Oral cavityLPTNF signaling pathway49/2418114/84656.51e-043.29e-032.12e-0349
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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
RPS6KA4SNVMissense_Mutationnovelc.2132N>Tp.Arg711Leup.R711LO75676protein_codingtolerated(0.19)benign(0.009)TCGA-A7-A0DB-01Breastbreast invasive carcinomaFemale<65I/IIHormone TherapyarimidexSD
RPS6KA4SNVMissense_Mutationnovelc.2134N>Tp.Gly712Cysp.G712CO75676protein_codingtolerated(0.21)benign(0.014)TCGA-A7-A0DB-01Breastbreast invasive carcinomaFemale<65I/IIHormone TherapyarimidexSD
RPS6KA4SNVMissense_Mutationnovelc.939N>Tp.Lys313Asnp.K313NO75676protein_codingdeleterious(0.03)benign(0.029)TCGA-AN-A046-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
RPS6KA4SNVMissense_Mutationc.1540G>Ap.Val514Metp.V514MO75676protein_codingdeleterious(0)probably_damaging(0.997)TCGA-AR-A1AH-01Breastbreast invasive carcinomaFemale<65I/IIUnspecificPD
RPS6KA4SNVMissense_Mutationc.1285N>Tp.Arg429Cysp.R429CO75676protein_codingtolerated(0.08)possibly_damaging(0.849)TCGA-D8-A1Y2-01Breastbreast invasive carcinomaFemale>=65I/IIHormone TherapytamoxiphenSD
RPS6KA4SNVMissense_Mutationnovelc.1225N>Ap.Glu409Lysp.E409KO75676protein_codingtolerated(0.11)benign(0.14)TCGA-2W-A8YY-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycisplatinCR
RPS6KA4SNVMissense_Mutationnovelc.2273C>Tp.Ser758Phep.S758FO75676protein_codingdeleterious_low_confidence(0.02)benign(0.063)TCGA-DS-A1OB-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycarboplatinPD
RPS6KA4SNVMissense_Mutationnovelc.1325N>Cp.Leu442Prop.L442PO75676protein_codingdeleterious(0)probably_damaging(0.934)TCGA-5M-AAT6-01Colorectumcolon adenocarcinomaFemale<65III/IVUnknownUnknownPD
RPS6KA4SNVMissense_Mutationc.1789G>Ap.Val597Ilep.V597IO75676protein_codingtolerated(0.12)probably_damaging(0.988)TCGA-A6-2686-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
RPS6KA4SNVMissense_Mutationnovelc.481N>Tp.Asp161Tyrp.D161YO75676protein_codingdeleterious(0)probably_damaging(0.999)TCGA-AA-A010-01Colorectumcolon adenocarcinomaFemale<65I/IIChemotherapyfolinicCR
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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
8986RPS6KA4SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, ENZYMEinhibitorHESPERADINHESPERADIN19035792
8986RPS6KA4SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, ENZYMEinhibitor252827421
8986RPS6KA4SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, ENZYMELINIFANIBLINIFANIB
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