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: USP9X

Gene summary for USP9X

Gene summary.

Gene information	Species	Human
	Gene symbol	USP9X
	Gene ID	8239
	Gene name	ubiquitin specific peptidase 9 X-linked
	Gene Alias	DFFRX
	Cytomap	Xp11.4
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q6P468

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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
8239	USP9X	HSIL_HPV_2	Human	Cervix	HSIL_HPV	6.17e-03	2.14e-01	0.0208
8239	USP9X	CCI_1	Human	Cervix	CC	3.97e-04	7.79e-01	0.528
8239	USP9X	CCI_2	Human	Cervix	CC	4.53e-11	1.74e+00	0.5249
8239	USP9X	CCI_3	Human	Cervix	CC	1.45e-05	8.63e-01	0.516
8239	USP9X	HTA11_3410_2000001011	Human	Colorectum	AD	2.12e-06	-4.52e-01	0.0155
8239	USP9X	HTA11_347_2000001011	Human	Colorectum	AD	3.75e-09	4.71e-01	-0.1954
8239	USP9X	HTA11_866_3004761011	Human	Colorectum	AD	6.58e-05	-4.31e-01	0.096
8239	USP9X	HTA11_7696_3000711011	Human	Colorectum	AD	2.56e-02	-3.42e-01	0.0674
8239	USP9X	HTA11_6818_2000001011	Human	Colorectum	AD	3.30e-02	-3.90e-01	0.0112
8239	USP9X	HTA11_99999970781_79442	Human	Colorectum	MSS	2.15e-03	-3.10e-01	0.294
8239	USP9X	HTA11_99999965104_69814	Human	Colorectum	MSS	3.87e-12	8.39e-01	0.281
8239	USP9X	A001-C-207	Human	Colorectum	FAP	1.08e-05	-3.85e-01	0.1278
8239	USP9X	A015-C-203	Human	Colorectum	FAP	2.66e-26	-4.39e-01	-0.1294
8239	USP9X	A015-C-204	Human	Colorectum	FAP	3.03e-06	-3.75e-01	-0.0228
8239	USP9X	A014-C-040	Human	Colorectum	FAP	1.52e-04	-5.52e-01	-0.1184
8239	USP9X	A002-C-201	Human	Colorectum	FAP	1.49e-08	-3.21e-01	0.0324
8239	USP9X	A001-C-119	Human	Colorectum	FAP	1.05e-06	-4.52e-01	-0.1557
8239	USP9X	A001-C-108	Human	Colorectum	FAP	5.81e-16	-3.39e-01	-0.0272
8239	USP9X	A002-C-205	Human	Colorectum	FAP	4.79e-20	-4.12e-01	-0.1236
8239	USP9X	A001-C-104	Human	Colorectum	FAP	1.62e-02	-2.78e-01	0.0184

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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:000762315	Prostate	Tumor	circadian rhythm	75/3246	210/18723	1.09e-10	6.79e-09	75
GO:001604916	Prostate	Tumor	cell growth	137/3246	482/18723	7.01e-10	3.51e-08	137
GO:007155915	Prostate	Tumor	response to transforming growth factor beta	76/3246	256/18723	6.86e-07	1.40e-05	76
GO:007156015	Prostate	Tumor	cellular response to transforming growth factor beta stimulus	72/3246	250/18723	4.47e-06	7.02e-05	72
GO:000717915	Prostate	Tumor	transforming growth factor beta receptor signaling pathway	58/3246	198/18723	2.11e-05	2.72e-04	58
GO:004275214	Prostate	Tumor	regulation of circadian rhythm	39/3246	121/18723	4.69e-05	5.21e-04	39
GO:005105413	Prostate	Tumor	positive regulation of DNA metabolic process	57/3246	201/18723	6.77e-05	7.21e-04	57
GO:000717815	Prostate	Tumor	transmembrane receptor protein serine/threonine kinase signaling pathway	90/3246	355/18723	7.93e-05	8.19e-04	90
GO:006156413	Prostate	Tumor	axon development	113/3246	467/18723	8.86e-05	8.74e-04	113
GO:005105212	Prostate	Tumor	regulation of DNA metabolic process	88/3246	359/18723	3.23e-04	2.59e-03	88
GO:000740913	Prostate	Tumor	axonogenesis	100/3246	418/18723	3.38e-04	2.70e-03	100
GO:004858814	Prostate	Tumor	developmental cell growth	60/3246	234/18723	8.41e-04	5.66e-03	60
GO:199000015	Prostate	Tumor	amyloid fibril formation	14/3246	34/18723	9.26e-04	6.10e-03	14
GO:006056014	Prostate	Tumor	developmental growth involved in morphogenesis	59/3246	234/18723	1.43e-03	8.84e-03	59
GO:004867514	Prostate	Tumor	axon extension	32/3246	120/18723	6.77e-03	3.09e-02	32
GO:199013814	Prostate	Tumor	neuron projection extension	43/3246	172/18723	6.83e-03	3.10e-02	43
GO:004851119	Skin	AK	rhythmic process	67/1910	298/18723	3.47e-10	4.37e-08	67
GO:006156416	Skin	AK	axon development	91/1910	467/18723	8.60e-10	8.63e-08	91
GO:001604920	Skin	AK	cell growth	93/1910	482/18723	9.55e-10	9.42e-08	93
GO:000762320	Skin	AK	circadian rhythm	51/1910	210/18723	2.80e-09	2.40e-07	51

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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

USP9X

SNV

Missense_Mutation

novel

c.1903N>A

p.Glu635Lys

p.E635K

Q93008

protein_coding

tolerated(0.3)

benign(0.009)

TCGA-5L-AAT0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

USP9X

SNV

Missense_Mutation

novel

c.6115N>A

p.Glu2039Lys

p.E2039K

Q93008

protein_coding

tolerated(0.05)

benign(0.33)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

USP9X

SNV

Missense_Mutation

c.1969N>T

p.Arg657Trp

p.R657W

Q93008

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A1-A0SP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

USP9X

SNV

Missense_Mutation

c.3418G>C

p.Asp1140His

p.D1140H

Q93008

protein_coding

deleterious(0.04)

probably_damaging(0.992)

TCGA-A2-A04W-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

USP9X

SNV

Missense_Mutation

c.6586N>G

p.Leu2196Val

p.L2196V

Q93008

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A7-A26J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

USP9X

SNV

Missense_Mutation

c.1795N>T

p.Arg599Cys

p.R599C

Q93008

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A8-A07W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

USP9X

SNV

Missense_Mutation

c.283N>C

p.Glu95Gln

p.E95Q

Q93008

protein_coding

deleterious(0.01)

probably_damaging(0.974)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP9X

SNV

Missense_Mutation

novel

c.1644G>T

p.Lys548Asn

p.K548N

Q93008

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP9X

SNV

Missense_Mutation

c.6172C>G

p.His2058Asp

p.H2058D

Q93008

protein_coding

deleterious(0)

benign(0.347)

TCGA-AN-A0G0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

USP9X

SNV

Missense_Mutation

rs371450770

c.3158N>T

p.Thr1053Met

p.T1053M

Q93008

protein_coding

deleterious(0.01)

possibly_damaging(0.487)

TCGA-AO-A0JD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

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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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