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:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:19021153	Cervix	CC	regulation of organelle assembly	40/2311	186/18723	2.92e-04	3.15e-03	40
GO:00705074	Cervix	CC	regulation of microtubule cytoskeleton organization	32/2311	148/18723	1.02e-03	8.51e-03	32
GO:00182054	Cervix	CC	peptidyl-lysine modification	62/2311	376/18723	1.04e-02	4.97e-02	62
GO:0043254	Colorectum	AD	regulation of protein-containing complex assembly	148/3918	428/18723	2.64e-11	3.18e-09	148
GO:0033044	Colorectum	AD	regulation of chromosome organization	60/3918	187/18723	2.25e-04	2.94e-03	60
GO:0007051	Colorectum	AD	spindle organization	58/3918	184/18723	4.71e-04	5.20e-03	58
GO:0051225	Colorectum	AD	spindle assembly	37/3918	117/18723	4.32e-03	2.96e-02	37
GO:0070507	Colorectum	AD	regulation of microtubule cytoskeleton organization	44/3918	148/18723	7.05e-03	4.31e-02	44
GO:0090169	Colorectum	AD	regulation of spindle assembly	11/3918	25/18723	7.89e-03	4.73e-02	11
GO:00432541	Colorectum	SER	regulation of protein-containing complex assembly	119/2897	428/18723	3.34e-11	5.86e-09	119
GO:00901691	Colorectum	SER	regulation of spindle assembly	10/2897	25/18723	2.70e-03	2.44e-02	10
GO:0090224	Colorectum	SER	regulation of spindle organization	13/2897	39/18723	4.39e-03	3.51e-02	13
GO:00432542	Colorectum	MSS	regulation of protein-containing complex assembly	130/3467	428/18723	1.38e-09	1.03e-07	130
GO:00330441	Colorectum	MSS	regulation of chromosome organization	55/3467	187/18723	1.86e-04	2.63e-03	55
GO:00070511	Colorectum	MSS	spindle organization	53/3467	184/18723	4.23e-04	5.19e-03	53
GO:00512251	Colorectum	MSS	spindle assembly	33/3467	117/18723	6.68e-03	4.38e-02	33
GO:00432544	Colorectum	FAP	regulation of protein-containing complex assembly	101/2622	428/18723	5.18e-08	4.07e-06	101
GO:00330442	Colorectum	FAP	regulation of chromosome organization	46/2622	187/18723	7.41e-05	1.36e-03	46
GO:00070512	Colorectum	FAP	spindle organization	41/2622	184/18723	1.50e-03	1.34e-02	41

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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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