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: ITCH

Gene summary for ITCH

Gene summary.

Gene information	Species	Human
	Gene symbol	ITCH
	Gene ID	83737
	Gene name	itchy E3 ubiquitin protein ligase
	Gene Alias	ADMFD
	Cytomap	20q11.22
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q96J02

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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
83737	ITCH	CCI_1	Human	Cervix	CC	2.46e-09	8.26e-01	0.528
83737	ITCH	CCI_2	Human	Cervix	CC	5.59e-10	1.02e+00	0.5249
83737	ITCH	CCI_3	Human	Cervix	CC	5.33e-13	9.13e-01	0.516
83737	ITCH	HTA11_3410_2000001011	Human	Colorectum	AD	1.31e-18	-6.41e-01	0.0155
83737	ITCH	HTA11_1938_2000001011	Human	Colorectum	AD	2.35e-02	-3.93e-01	-0.0811
83737	ITCH	HTA11_78_2000001011	Human	Colorectum	AD	7.62e-03	-4.53e-01	-0.1088
83737	ITCH	HTA11_3361_2000001011	Human	Colorectum	AD	3.17e-04	-4.55e-01	-0.1207
83737	ITCH	HTA11_696_2000001011	Human	Colorectum	AD	6.84e-06	-3.67e-01	-0.1464
83737	ITCH	HTA11_866_2000001011	Human	Colorectum	AD	1.52e-06	-3.94e-01	-0.1001
83737	ITCH	HTA11_7862_2000001011	Human	Colorectum	AD	2.36e-02	-5.69e-01	-0.0179
83737	ITCH	HTA11_866_3004761011	Human	Colorectum	AD	2.20e-13	-6.14e-01	0.096
83737	ITCH	HTA11_10711_2000001011	Human	Colorectum	AD	1.35e-08	-6.31e-01	0.0338
83737	ITCH	HTA11_7696_3000711011	Human	Colorectum	AD	3.77e-16	-5.41e-01	0.0674
83737	ITCH	HTA11_6818_2000001021	Human	Colorectum	AD	8.59e-04	-5.43e-01	0.0588
83737	ITCH	HTA11_99999970781_79442	Human	Colorectum	MSS	4.32e-17	-5.43e-01	0.294
83737	ITCH	HTA11_99999974143_84620	Human	Colorectum	MSS	1.84e-16	-4.85e-01	0.3005
83737	ITCH	A015-C-203	Human	Colorectum	FAP	4.87e-32	-4.80e-01	-0.1294
83737	ITCH	A015-C-204	Human	Colorectum	FAP	1.12e-08	-3.82e-01	-0.0228
83737	ITCH	A014-C-040	Human	Colorectum	FAP	1.28e-04	-4.70e-01	-0.1184
83737	ITCH	A002-C-201	Human	Colorectum	FAP	2.83e-14	-3.93e-01	0.0324

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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
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:19030382	Oral cavity	EOLP	negative regulation of leukocyte cell-cell adhesion	33/2218	141/18723	8.63e-05	1.02e-03	33
GO:00329445	Oral cavity	EOLP	regulation of mononuclear cell proliferation	47/2218	227/18723	8.81e-05	1.04e-03	47
GO:004311223	Oral cavity	EOLP	receptor metabolic process	37/2218	166/18723	1.00e-04	1.14e-03	37
GO:004664011	Oral cavity	EOLP	regulation of alpha-beta T cell proliferation	13/2218	35/18723	1.03e-04	1.17e-03	13
GO:00508663	Oral cavity	EOLP	negative regulation of cell activation	44/2218	210/18723	1.09e-04	1.23e-03	44
GO:004340924	Oral cavity	EOLP	negative regulation of MAPK cascade	39/2218	180/18723	1.25e-04	1.38e-03	39
GO:00321023	Oral cavity	EOLP	negative regulation of response to external stimulus	75/2218	420/18723	1.74e-04	1.80e-03	75
GO:003109824	Oral cavity	EOLP	stress-activated protein kinase signaling cascade	49/2218	247/18723	1.89e-04	1.94e-03	49
GO:004663311	Oral cavity	EOLP	alpha-beta T cell proliferation	13/2218	38/18723	2.68e-04	2.58e-03	13
GO:00026953	Oral cavity	EOLP	negative regulation of leukocyte activation	39/2218	187/18723	2.89e-04	2.74e-03	39
GO:005140324	Oral cavity	EOLP	stress-activated MAPK cascade	47/2218	239/18723	3.11e-04	2.91e-03	47
GO:004212910	Oral cavity	EOLP	regulation of T cell proliferation	36/2218	171/18723	4.01e-04	3.58e-03	36
GO:00508681	Oral cavity	EOLP	negative regulation of T cell activation	28/2218	122/18723	4.03e-04	3.58e-03	28
GO:007053412	Oral cavity	EOLP	protein K63-linked ubiquitination	16/2218	56/18723	5.70e-04	4.82e-03	16
GO:007030224	Oral cavity	EOLP	regulation of stress-activated protein kinase signaling cascade	39/2218	195/18723	6.89e-04	5.70e-03	39
GO:007064611	Oral cavity	EOLP	protein modification by small protein removal	33/2218	157/18723	7.04e-04	5.78e-03	33
GO:005170126	Oral cavity	EOLP	biological process involved in interaction with host	40/2218	203/18723	8.05e-04	6.31e-03	40
GO:003280113	Oral cavity	EOLP	receptor catabolic process	10/2218	28/18723	9.28e-04	7.08e-03	10
GO:0046636	Oral cavity	EOLP	negative regulation of alpha-beta T cell activation	13/2218	43/18723	1.03e-03	7.63e-03	13
GO:00320881	Oral cavity	EOLP	negative regulation of NF-kappaB transcription factor activity	22/2218	93/18723	1.05e-03	7.77e-03	22

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0493218	Cervix	CC	Non-alcoholic fatty liver disease	58/1267	155/8465	3.58e-12	1.05e-10	6.23e-11	58
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0414418	Cervix	CC	Endocytosis	64/1267	251/8465	6.97e-06	6.10e-05	3.61e-05	64
hsa046686	Cervix	CC	TNF signaling pathway	28/1267	114/8465	4.60e-03	1.62e-02	9.59e-03	28
hsa04330	Cervix	CC	Notch signaling pathway	17/1267	62/8465	7.99e-03	2.56e-02	1.51e-02	17
hsa0493219	Cervix	CC	Non-alcoholic fatty liver disease	58/1267	155/8465	3.58e-12	1.05e-10	6.23e-11	58
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0414419	Cervix	CC	Endocytosis	64/1267	251/8465	6.97e-06	6.10e-05	3.61e-05	64
hsa0466813	Cervix	CC	TNF signaling pathway	28/1267	114/8465	4.60e-03	1.62e-02	9.59e-03	28
hsa043301	Cervix	CC	Notch signaling pathway	17/1267	62/8465	7.99e-03	2.56e-02	1.51e-02	17
hsa04932	Colorectum	AD	Non-alcoholic fatty liver disease	90/2092	155/8465	4.83e-19	1.80e-17	1.15e-17	90
hsa04144	Colorectum	AD	Endocytosis	111/2092	251/8465	5.95e-12	1.42e-10	9.08e-11	111
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa049321	Colorectum	AD	Non-alcoholic fatty liver disease	90/2092	155/8465	4.83e-19	1.80e-17	1.15e-17	90
hsa041441	Colorectum	AD	Endocytosis	111/2092	251/8465	5.95e-12	1.42e-10	9.08e-11	111
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa049324	Colorectum	MSS	Non-alcoholic fatty liver disease	85/1875	155/8465	4.19e-19	1.17e-17	7.17e-18	85
hsa041444	Colorectum	MSS	Endocytosis	102/1875	251/8465	1.85e-11	4.43e-10	2.71e-10	102
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa049325	Colorectum	MSS	Non-alcoholic fatty liver disease	85/1875	155/8465	4.19e-19	1.17e-17	7.17e-18	85

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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

ITCH

SNV

Missense_Mutation

c.673G>A

p.Glu225Lys

p.E225K

Q96J02

protein_coding

tolerated(0.51)

benign(0.293)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ITCH

SNV

Missense_Mutation

c.673G>A

p.Glu225Lys

p.E225K

Q96J02

protein_coding

tolerated(0.51)

benign(0.293)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITCH

SNV

Missense_Mutation

novel

c.1286N>T

p.Ser429Leu

p.S429L

Q96J02

protein_coding

tolerated(0.27)

benign(0.017)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ITCH

SNV

Missense_Mutation

novel

c.2439N>T

p.Trp813Cys

p.W813C

Q96J02

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E9-A5UO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ITCH

SNV

Missense_Mutation

novel

c.2605N>T

p.His869Tyr

p.H869Y

Q96J02

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-WT-AB41-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

ITCH

SNV

Missense_Mutation

novel

c.1657N>G

p.Thr553Ala

p.T553A

Q96J02

protein_coding

deleterious(0.04)

benign(0.011)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ITCH

SNV

Missense_Mutation

novel

c.607N>A

p.Gln203Lys

p.Q203K

Q96J02

protein_coding

tolerated(0.95)

benign(0)

TCGA-C5-A7XC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ITCH

SNV

Missense_Mutation

novel

c.787N>C

p.Thr263Pro

p.T263P

Q96J02

protein_coding

tolerated(0.25)

probably_damaging(0.998)

TCGA-DS-A7WH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ITCH

SNV

Missense_Mutation

c.2399N>C

p.Arg800Pro

p.R800P

Q96J02

protein_coding

deleterious(0)

probably_damaging(0.987)

TCGA-EA-A3HT-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

ITCH

SNV

Missense_Mutation

c.719N>G

p.Ser240Cys

p.S240C

Q96J02

protein_coding

deleterious(0.04)

probably_damaging(0.998)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

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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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