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: PDE4D

Gene summary for PDE4D

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

PDE4D

Gene ID

5144

Gene namephosphodiesterase 4D
Gene AliasACRDYS2
Cytomap5q11.2-q12.1
Gene Typeprotein-coding
GO ID

GO:0001816

UniProtAcc

A0A140VJR0


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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
5144PDE4DCCI_1HumanCervixCC1.42e-049.22e-010.528
5144PDE4DCCI_3HumanCervixCC8.93e-291.69e+000.516
5144PDE4DCCII_1HumanCervixCC2.14e-197.87e-010.3249
5144PDE4DT1HumanCervixCC1.83e-063.73e-010.0918
5144PDE4DHTA11_3410_2000001011HumanColorectumAD1.56e-10-4.59e-010.0155
5144PDE4DHTA11_2951_2000001011HumanColorectumAD6.29e-05-6.37e-010.0216
5144PDE4DHTA11_78_2000001011HumanColorectumAD4.09e-118.08e-01-0.1088
5144PDE4DHTA11_347_2000001011HumanColorectumAD6.25e-259.88e-01-0.1954
5144PDE4DHTA11_411_2000001011HumanColorectumSER6.02e-251.17e+00-0.2602
5144PDE4DHTA11_2112_2000001011HumanColorectumSER2.56e-024.98e-01-0.2196
5144PDE4DHTA11_2992_2000001011HumanColorectumSER8.22e-065.08e-01-0.1706
5144PDE4DHTA11_5212_2000001011HumanColorectumAD2.19e-023.51e-01-0.2061
5144PDE4DHTA11_7696_3000711011HumanColorectumAD1.69e-07-4.19e-010.0674
5144PDE4DHTA11_99999970781_79442HumanColorectumMSS8.87e-09-3.65e-010.294
5144PDE4DHTA11_99999965062_69753HumanColorectumMSI-H1.79e-181.73e+000.3487
5144PDE4DHTA11_99999965104_69814HumanColorectumMSS2.73e-024.45e-010.281
5144PDE4DHTA11_99999971662_82457HumanColorectumMSS1.53e-06-1.58e-010.3859
5144PDE4DHTA11_99999973899_84307HumanColorectumMSS1.54e-11-8.28e-010.2585
5144PDE4DHTA11_99999974143_84620HumanColorectumMSS6.73e-55-1.08e+000.3005
5144PDE4DA015-C-203HumanColorectumFAP6.36e-47-7.12e-01-0.1294
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
CervixThe 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.CC: Cervix cancer
HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
N_HPV: HPV-infected normal cervix
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
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
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
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:003297010CervixCCregulation of actin filament-based process96/2311397/187234.00e-118.54e-0996
GO:00512359CervixCCmaintenance of location78/2311327/187235.18e-094.92e-0778
GO:005165110CervixCCmaintenance of location in cell55/2311214/187236.63e-083.85e-0655
GO:00027644CervixCCimmune response-regulating signaling pathway97/2311468/187231.49e-077.07e-0697
GO:00018197CervixCCpositive regulation of cytokine production95/2311467/187234.88e-071.85e-0595
GO:004593610CervixCCnegative regulation of phosphate metabolic process88/2311441/187232.92e-068.27e-0588
GO:001056310CervixCCnegative regulation of phosphorus metabolic process88/2311442/187233.21e-068.77e-0588
GO:004232610CervixCCnegative regulation of phosphorylation77/2311385/187231.09e-052.38e-0477
GO:000193310CervixCCnegative regulation of protein phosphorylation69/2311342/187232.29e-054.01e-0469
GO:00181057CervixCCpeptidyl-serine phosphorylation63/2311315/187236.65e-059.47e-0463
GO:00022533CervixCCactivation of immune response72/2311375/187238.26e-051.11e-0372
GO:00182096CervixCCpeptidyl-serine modification66/2311338/187239.58e-051.25e-0366
GO:00106444CervixCCcell communication by electrical coupling12/231132/187232.53e-042.79e-0312
GO:00106494CervixCCregulation of cell communication by electrical coupling8/231116/187232.73e-042.99e-038
GO:00467008CervixCCheterocycle catabolic process80/2311445/187233.23e-043.42e-0380
GO:00346559CervixCCnucleobase-containing compound catabolic process74/2311407/187233.77e-043.88e-0374
GO:000206410CervixCCepithelial cell development45/2311220/187234.14e-044.21e-0345
GO:00196939CervixCCribose phosphate metabolic process72/2311396/187234.49e-044.48e-0372
GO:00092599CervixCCribonucleotide metabolic process70/2311385/187235.35e-045.18e-0370
GO:0002768CervixCCimmune response-regulating cell surface receptor signaling pathway59/2311315/187236.64e-046.11e-0359
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa0492812CervixCCParathyroid hormone synthesis, secretion and action27/1267106/84653.12e-031.19e-027.03e-0327
hsa0492813CervixCCParathyroid hormone synthesis, secretion and action27/1267106/84653.12e-031.19e-027.03e-0327
hsa04928ColorectumADParathyroid hormone synthesis, secretion and action38/2092106/84656.60e-032.77e-021.76e-0238
hsa049281ColorectumADParathyroid hormone synthesis, secretion and action38/2092106/84656.60e-032.77e-021.76e-0238
hsa049282ColorectumSERParathyroid hormone synthesis, secretion and action31/1580106/84655.20e-033.28e-022.38e-0231
hsa049283ColorectumSERParathyroid hormone synthesis, secretion and action31/1580106/84655.20e-033.28e-022.38e-0231
hsa049284ColorectumMSSParathyroid hormone synthesis, secretion and action37/1875106/84651.72e-039.13e-035.59e-0337
hsa049285ColorectumMSSParathyroid hormone synthesis, secretion and action37/1875106/84651.72e-039.13e-035.59e-0337
hsa049286ColorectumFAPParathyroid hormone synthesis, secretion and action29/1404106/84653.37e-031.44e-028.77e-0329
hsa04024ColorectumFAPcAMP signaling pathway51/1404225/84651.02e-023.68e-022.24e-0251
hsa049287ColorectumFAPParathyroid hormone synthesis, secretion and action29/1404106/84653.37e-031.44e-028.77e-0329
hsa040241ColorectumFAPcAMP signaling pathway51/1404225/84651.02e-023.68e-022.24e-0251
hsa040242ColorectumCRCcAMP signaling pathway47/1091225/84654.57e-044.77e-033.23e-0347
hsa049288ColorectumCRCParathyroid hormone synthesis, secretion and action24/1091106/84653.71e-032.29e-021.55e-0224
hsa040243ColorectumCRCcAMP signaling pathway47/1091225/84654.57e-044.77e-033.23e-0347
hsa049289ColorectumCRCParathyroid hormone synthesis, secretion and action24/1091106/84653.71e-032.29e-021.55e-0224
hsa0492816EsophagusESCCParathyroid hormone synthesis, secretion and action66/4205106/84655.86e-031.47e-027.51e-0366
hsa0492817EsophagusESCCParathyroid hormone synthesis, secretion and action66/4205106/84655.86e-031.47e-027.51e-0366
hsa0492810LungIACParathyroid hormone synthesis, secretion and action26/1053106/84654.34e-044.03e-032.68e-0326
hsa0492811LungIACParathyroid hormone synthesis, secretion and action26/1053106/84654.34e-044.03e-032.68e-0326
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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
PDE4DSNVMissense_Mutationc.647T>Cp.Ile216Thrp.I216TQ08499protein_codingtolerated_low_confidence(0.29)possibly_damaging(0.84)TCGA-A8-A09C-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
PDE4DSNVMissense_Mutationc.1895N>Ap.Arg632Hisp.R632HQ08499protein_codingdeleterious_low_confidence(0)probably_damaging(0.985)TCGA-A8-A09Z-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
PDE4DSNVMissense_Mutationc.1904N>Tp.Thr635Metp.T635MQ08499protein_codingdeleterious_low_confidence(0)probably_damaging(1)TCGA-AN-A0AJ-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
PDE4DSNVMissense_Mutationc.896N>Ap.Ser299Tyrp.S299YQ08499protein_codingdeleterious_low_confidence(0)probably_damaging(0.974)TCGA-BH-A0BP-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
PDE4DSNVMissense_Mutationc.1691N>Gp.Lys564Argp.K564RQ08499protein_codingtolerated_low_confidence(0.27)probably_damaging(0.97)TCGA-BH-A18T-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownPD
PDE4DSNVMissense_Mutationc.1291N>Tp.Arg431Trpp.R431WQ08499protein_codingdeleterious_low_confidence(0)probably_damaging(0.994)TCGA-C8-A1HL-01Breastbreast invasive carcinomaFemale<65III/IVUnknownUnknownSD
PDE4DSNVMissense_Mutationc.2221G>Cp.Glu741Glnp.E741QQ08499protein_codingdeleterious_low_confidence(0.01)probably_damaging(0.954)TCGA-E2-A159-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapycyclophosphamideSD
PDE4DinsertionNonsense_Mutationnovelc.1924_1925insGTTGTTGTTGAAAATAGTGACAATTTTACCAAACTAAGTTTAGp.Phe642CysfsTer4p.F642Cfs*4Q08499protein_codingTCGA-A2-A0D1-01Breastbreast invasive carcinomaFemale>=65I/IIChemotherapytaxotereSD
PDE4DdeletionFrame_Shift_Delnovelc.2148delNp.Ser717LeufsTer22p.S717Lfs*22Q08499protein_codingTCGA-EW-A2FV-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapydocetaxelSD
PDE4DSNVMissense_Mutationnovelc.359N>Tp.Ala120Valp.A120VQ08499protein_codingtolerated_low_confidence(0.24)benign(0.058)TCGA-VS-A8EH-01Cervixcervical & endocervical cancerFemale<65III/IVChemotherapycisplatinCR
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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
5144PDE4DDRUGGABLE GENOME, ENZYMEinhibitorCHEMBL932DIPYRIDAMOLE
5144PDE4DDRUGGABLE GENOME, ENZYMEGPD-1116
5144PDE4DDRUGGABLE GENOME, ENZYMEDENBUFYLLINEDENBUFYLLINE
5144PDE4DDRUGGABLE GENOME, ENZYMEBPN14770BPN-14770
5144PDE4DDRUGGABLE GENOME, ENZYMEROLIPRAMROLIPRAM
5144PDE4DDRUGGABLE GENOME, ENZYMEOglemilastOGLEMILAST18660832
5144PDE4DDRUGGABLE GENOME, ENZYMEinhibitorCHEMBL1370561AMINOPHYLLINE
5144PDE4DDRUGGABLE GENOME, ENZYMEinhibitorCHEMBL484785CRISABOROLE
5144PDE4DDRUGGABLE GENOME, ENZYMEAN-2898
5144PDE4DDRUGGABLE GENOME, ENZYMEinhibitorCHEMBL193240ROFLUMILAST
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