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: USP47

Gene summary for USP47

Gene summary.

Gene information	Species	Human
	Gene symbol	USP47
	Gene ID	55031
	Gene name	ubiquitin specific peptidase 47
	Gene Alias	TRFP
	Cytomap	11p15.3
	Gene Type	protein-coding
	GO ID	GO:0000086
	UniProtAcc	Q68D97

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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
55031	USP47	CCI_2	Human	Cervix	CC	5.49e-03	5.13e-01	0.5249
55031	USP47	CCI_3	Human	Cervix	CC	1.60e-03	5.47e-01	0.516
55031	USP47	HTA11_3410_2000001011	Human	Colorectum	AD	7.18e-16	-6.56e-01	0.0155
55031	USP47	HTA11_2487_2000001011	Human	Colorectum	SER	3.48e-03	-5.42e-01	-0.1808
55031	USP47	HTA11_3361_2000001011	Human	Colorectum	AD	2.20e-08	-7.41e-01	-0.1207
55031	USP47	HTA11_696_2000001011	Human	Colorectum	AD	7.07e-18	-5.53e-01	-0.1464
55031	USP47	HTA11_866_2000001011	Human	Colorectum	AD	9.10e-15	-4.79e-01	-0.1001
55031	USP47	HTA11_1391_2000001011	Human	Colorectum	AD	1.35e-02	-4.22e-01	-0.059
55031	USP47	HTA11_5212_2000001011	Human	Colorectum	AD	5.25e-03	-7.51e-01	-0.2061
55031	USP47	HTA11_546_2000001011	Human	Colorectum	AD	2.27e-02	-4.79e-01	-0.0842
55031	USP47	HTA11_866_3004761011	Human	Colorectum	AD	2.98e-12	-6.71e-01	0.096
55031	USP47	HTA11_8622_2000001021	Human	Colorectum	SER	1.83e-02	-6.95e-01	0.0528
55031	USP47	HTA11_10711_2000001011	Human	Colorectum	AD	9.32e-07	-6.27e-01	0.0338
55031	USP47	HTA11_7696_3000711011	Human	Colorectum	AD	2.14e-21	-5.54e-01	0.0674
55031	USP47	HTA11_6818_2000001021	Human	Colorectum	AD	3.64e-04	-6.33e-01	0.0588
55031	USP47	HTA11_99999970781_79442	Human	Colorectum	MSS	6.31e-06	-3.74e-01	0.294
55031	USP47	HTA11_99999971662_82457	Human	Colorectum	MSS	1.52e-09	-4.39e-01	0.3859
55031	USP47	HTA11_99999973899_84307	Human	Colorectum	MSS	5.62e-05	-6.66e-01	0.2585
55031	USP47	HTA11_99999974143_84620	Human	Colorectum	MSS	1.58e-25	-6.47e-01	0.3005
55031	USP47	A015-C-203	Human	Colorectum	FAP	6.69e-28	-2.14e-01	-0.1294

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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:0016055	Colorectum	AD	Wnt signaling pathway	130/3918	444/18723	1.60e-05	3.37e-04	130
GO:0198738	Colorectum	AD	cell-cell signaling by wnt	130/3918	446/18723	2.02e-05	4.10e-04	130
GO:0045861	Colorectum	AD	negative regulation of proteolysis	106/3918	351/18723	2.33e-05	4.57e-04	106
GO:2001020	Colorectum	AD	regulation of response to DNA damage stimulus	71/3918	219/18723	4.38e-05	7.65e-04	71
GO:0052548	Colorectum	AD	regulation of endopeptidase activity	124/3918	432/18723	6.58e-05	1.07e-03	124
GO:0060070	Colorectum	AD	canonical Wnt signaling pathway	90/3918	303/18723	1.76e-04	2.38e-03	90
GO:0060828	Colorectum	AD	regulation of canonical Wnt signaling pathway	77/3918	253/18723	2.19e-04	2.87e-03	77
GO:0009410	Colorectum	AD	response to xenobiotic stimulus	128/3918	462/18723	2.69e-04	3.31e-03	128
GO:0043154	Colorectum	AD	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	30/3918	78/18723	2.95e-04	3.59e-03	30
GO:0030307	Colorectum	AD	positive regulation of cell growth	54/3918	166/18723	3.08e-04	3.69e-03	54
GO:0045927	Colorectum	AD	positive regulation of growth	77/3918	259/18723	4.82e-04	5.27e-03	77
GO:2000117	Colorectum	AD	negative regulation of cysteine-type endopeptidase activity	31/3918	86/18723	8.67e-04	8.45e-03	31
GO:0030177	Colorectum	AD	positive regulation of Wnt signaling pathway	45/3918	140/18723	1.23e-03	1.09e-02	45
GO:0008630	Colorectum	AD	intrinsic apoptotic signaling pathway in response to DNA damage	33/3918	99/18723	2.71e-03	2.05e-02	33
GO:0007346	Colorectum	AD	regulation of mitotic cell cycle	119/3918	457/18723	4.60e-03	3.14e-02	119
GO:20012421	Colorectum	SER	regulation of intrinsic apoptotic signaling pathway	59/2897	164/18723	8.42e-11	1.20e-08	59
GO:00971931	Colorectum	SER	intrinsic apoptotic signaling pathway	87/2897	288/18723	1.67e-10	2.32e-08	87
GO:20012331	Colorectum	SER	regulation of apoptotic signaling pathway	101/2897	356/18723	3.05e-10	4.07e-08	101
GO:00316471	Colorectum	SER	regulation of protein stability	86/2897	298/18723	2.56e-09	2.42e-07	86
GO:00525471	Colorectum	SER	regulation of peptidase activity	114/2897	461/18723	1.18e-07	7.17e-06	114

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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

USP47

SNV

Missense_Mutation

rs754155092

c.2314N>T

p.Arg772Cys

p.R772C

Q96K76

protein_coding

deleterious(0)

probably_damaging(0.965)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP47

SNV

Missense_Mutation

c.3127N>C

p.Glu1043Gln

p.E1043Q

Q96K76

protein_coding

tolerated(0.25)

benign(0.047)

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP47

SNV

Missense_Mutation

novel

c.81N>C

p.Met27Ile

p.M27I

Q96K76

protein_coding

tolerated_low_confidence(0.19)

benign(0)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

USP47

SNV

Missense_Mutation

c.4046G>A

p.Arg1349His

p.R1349H

Q96K76

protein_coding

tolerated(0.09)

benign(0)

TCGA-BH-A18F-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

USP47

SNV

Missense_Mutation

c.3865C>T

p.His1289Tyr

p.H1289Y

Q96K76

protein_coding

deleterious(0.01)

benign(0.101)

TCGA-C8-A12Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

USP47

SNV

Missense_Mutation

c.2879N>G

p.Asp960Gly

p.D960G

Q96K76

protein_coding

tolerated(0.06)

probably_damaging(0.971)

TCGA-D8-A27I-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adrimycin+cyclophosphamide

USP47

SNV

Missense_Mutation

c.1726N>C

p.Asp576His

p.D576H

Q96K76

protein_coding

tolerated(0.1)

benign(0)

TCGA-EW-A1P4-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

USP47

SNV

Missense_Mutation

novel

c.3742G>C

p.Glu1248Gln

p.E1248Q

Q96K76

protein_coding

deleterious(0.04)

probably_damaging(0.954)

TCGA-LD-A74U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

taxotere

USP47

insertion

Frame_Shift_Ins

novel

c.3125_3126insGTCCCTC

p.Asp1042GlufsTer4

p.D1042Efs*4

Q96K76

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP47

SNV

Missense_Mutation

novel

c.1153N>A

p.Leu385Met

p.L385M

Q96K76

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-2W-A8YY-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

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