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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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: SENP6

Gene summary for SENP6

Gene summary.

Gene information	Species	Human
	Gene symbol	SENP6
	Gene ID	26054
	Gene name	SUMO specific peptidase 6
	Gene Alias	SSP1
	Cytomap	6q14.1
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	B3KMM0

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Malignant transformation analysis

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

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
26054	SENP6	CA_HPV_1	Human	Cervix	CC	1.56e-03	-6.14e-02	0.0264
26054	SENP6	CCI_2	Human	Cervix	CC	1.21e-06	7.32e-01	0.5249
26054	SENP6	CCI_3	Human	Cervix	CC	7.60e-07	8.58e-01	0.516
26054	SENP6	HTA11_3410_2000001011	Human	Colorectum	AD	2.95e-33	-7.72e-01	0.0155
26054	SENP6	HTA11_2487_2000001011	Human	Colorectum	SER	2.44e-05	-5.35e-01	-0.1808
26054	SENP6	HTA11_2951_2000001011	Human	Colorectum	AD	2.56e-02	-7.74e-01	0.0216
26054	SENP6	HTA11_2112_2000001011	Human	Colorectum	SER	2.11e-02	-7.76e-01	-0.2196
26054	SENP6	HTA11_3361_2000001011	Human	Colorectum	AD	3.70e-13	-7.94e-01	-0.1207
26054	SENP6	HTA11_696_2000001011	Human	Colorectum	AD	1.09e-12	-4.70e-01	-0.1464
26054	SENP6	HTA11_5212_2000001011	Human	Colorectum	AD	9.96e-06	-7.20e-01	-0.2061
26054	SENP6	HTA11_9341_2000001011	Human	Colorectum	SER	5.74e-03	-8.27e-01	-0.00410000000000005
26054	SENP6	HTA11_866_3004761011	Human	Colorectum	AD	1.34e-08	-5.19e-01	0.096
26054	SENP6	HTA11_9408_2000001011	Human	Colorectum	AD	2.47e-02	-7.44e-01	0.0451
26054	SENP6	HTA11_8622_2000001021	Human	Colorectum	SER	1.73e-03	-6.80e-01	0.0528
26054	SENP6	HTA11_10711_2000001011	Human	Colorectum	AD	4.43e-04	-4.30e-01	0.0338
26054	SENP6	HTA11_7696_3000711011	Human	Colorectum	AD	1.03e-04	-3.62e-01	0.0674
26054	SENP6	HTA11_11156_2000001011	Human	Colorectum	AD	1.51e-02	-8.11e-01	0.0397
26054	SENP6	HTA11_99999970781_79442	Human	Colorectum	MSS	1.71e-04	-3.59e-01	0.294
26054	SENP6	HTA11_99999971662_82457	Human	Colorectum	MSS	6.30e-08	-4.06e-01	0.3859
26054	SENP6	HTA11_99999973899_84307	Human	Colorectum	MSS	3.95e-03	-5.53e-01	0.2585

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		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

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗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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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:00513822	Skin	cSCC	kinetochore assembly	11/4864	18/18723	1.74e-03	1.06e-02	11
GO:003288612	Skin	cSCC	regulation of microtubule-based process	82/4864	240/18723	2.82e-03	1.58e-02	82
GO:00169255	Skin	cSCC	protein sumoylation	23/4864	53/18723	4.39e-03	2.29e-02	23
GO:00706464	Skin	cSCC	protein modification by small protein removal	55/4864	157/18723	7.29e-03	3.46e-02	55
GO:00901698	Thyroid	HT	regulation of spindle assembly	9/1272	25/18723	2.26e-05	5.09e-04	9
GO:004325430	Thyroid	HT	regulation of protein-containing complex assembly	50/1272	428/18723	1.24e-04	2.00e-03	50
GO:00902247	Thyroid	HT	regulation of spindle organization	10/1272	39/18723	2.09e-04	3.01e-03	10
GO:00512258	Thyroid	HT	spindle assembly	17/1272	117/18723	2.34e-03	2.00e-02	17
GO:19021158	Thyroid	HT	regulation of organelle assembly	23/1272	186/18723	3.89e-03	2.88e-02	23
GO:007050710	Thyroid	HT	regulation of microtubule cytoskeleton organization	19/1272	148/18723	5.50e-03	3.62e-02	19
GO:000705110	Thyroid	HT	spindle organization	22/1272	184/18723	6.95e-03	4.22e-02	22
GO:003304418	Thyroid	HT	regulation of chromosome organization	22/1272	187/18723	8.36e-03	4.79e-02	22
GO:0043254113	Thyroid	PTC	regulation of protein-containing complex assembly	215/5968	428/18723	1.23e-15	9.09e-14	215
GO:00182059	Thyroid	PTC	peptidyl-lysine modification	188/5968	376/18723	1.34e-13	7.09e-12	188
GO:003304419	Thyroid	PTC	regulation of chromosome organization	102/5968	187/18723	1.04e-10	3.58e-09	102
GO:007050717	Thyroid	PTC	regulation of microtubule cytoskeleton organization	80/5968	148/18723	1.79e-08	4.19e-07	80
GO:000705116	Thyroid	PTC	spindle organization	92/5968	184/18723	2.21e-07	3.92e-06	92
GO:190211516	Thyroid	PTC	regulation of organelle assembly	88/5968	186/18723	7.41e-06	8.65e-05	88
GO:00328866	Thyroid	PTC	regulation of microtubule-based process	105/5968	240/18723	6.91e-05	6.03e-04	105
GO:00169256	Thyroid	PTC	protein sumoylation	30/5968	53/18723	1.71e-04	1.31e-03	30

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon 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

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

SENP6

SNV

Missense_Mutation

c.1471C>G

p.Leu491Val

p.L491V

Q9GZR1

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-A2-A0YH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

SENP6

SNV

Missense_Mutation

rs550031341

c.1316N>T

p.Ser439Phe

p.S439F

Q9GZR1

protein_coding

deleterious(0.01)

possibly_damaging(0.45)

TCGA-AC-A2B8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

chemo

SENP6

SNV

Missense_Mutation

novel

c.3139C>T

p.Leu1047Phe

p.L1047F

Q9GZR1

protein_coding

tolerated(0.13)

benign(0.051)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SENP6

SNV

Missense_Mutation

novel

c.1543N>G

p.Gln515Glu

p.Q515E

Q9GZR1

protein_coding

tolerated(0.3)

benign(0.003)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SENP6

insertion

Frame_Shift_Ins

novel

c.2597_2598insAGCTGGAATGCTGTGGCACAATCTCGGCTCACTGCAACCTCTGCCTC

p.His866GlnfsTer50

p.H866Qfs*50

Q9GZR1

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

SENP6

insertion

In_Frame_Ins

novel

c.2667_2668insTATGTTATT

p.Lys889_Ser890insTyrValIle

p.K889_S890insYVI

Q9GZR1

protein_coding

TCGA-AR-A0U2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

SENP6

SNV

Missense_Mutation

c.1126N>A

p.Glu376Lys

p.E376K

Q9GZR1

protein_coding

tolerated(0.09)

possibly_damaging(0.544)

TCGA-C5-A901-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SENP6

SNV

Missense_Mutation

c.1276N>G

p.Gln426Glu

p.Q426E

Q9GZR1

protein_coding

tolerated(0.08)

benign(0.08)

TCGA-DS-A0VM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SENP6

SNV

Missense_Mutation

novel

c.1355N>G

p.Val452Gly

p.V452G

Q9GZR1

protein_coding

deleterious(0)

possibly_damaging(0.791)

TCGA-MA-AA43-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

SENP6

SNV

Missense_Mutation

novel

c.2254G>C

p.Glu752Gln

p.E752Q

Q9GZR1

protein_coding

tolerated(0.91)

benign(0.241)

TCGA-VS-A9U6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
26054	SENP6	ENZYME, PROTEASE, DRUGGABLE GENOME		GNF-PF-1702	CHEMBL600313
26054	SENP6	ENZYME, PROTEASE, DRUGGABLE GENOME		CID 4101591	CHEMBL428789
26054	SENP6	ENZYME, PROTEASE, DRUGGABLE GENOME		DNDI1417156	CHEMBL1504679
26054	SENP6	ENZYME, PROTEASE, DRUGGABLE GENOME		DIHYDROXANTHOHUMOL	DIHYDROXANTHOHUMOL
26054	SENP6	ENZYME, PROTEASE, DRUGGABLE GENOME		IPRIFLAVONE	IPRIFLAVONE
26054	SENP6	ENZYME, PROTEASE, DRUGGABLE GENOME		XANTHOANGELOL B	XANTHOANGELOL B
26054	SENP6	ENZYME, PROTEASE, DRUGGABLE GENOME		4-PHENYLAMINO-[1,2]NAPHTHOQUINONE	CHEMBL299853
26054	SENP6	ENZYME, PROTEASE, DRUGGABLE GENOME		6,4'-DIHYDROXYFLAVONE	CHEMBL484663
26054	SENP6	ENZYME, PROTEASE, DRUGGABLE GENOME		2-(4-NITROBENZYLSULFANYL)BENZOXAZOLE	CHEMBL412603
26054	SENP6	ENZYME, PROTEASE, DRUGGABLE GENOME		BAS-0338868	CHEMBL378903

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