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: HUWE1

Gene summary for HUWE1

Gene summary.

Gene information	Species	Human
	Gene symbol	HUWE1
	Gene ID	10075
	Gene name	HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1
	Gene Alias	ARF-BP1
	Cytomap	Xp11.22
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	A0A024R9W5

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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
10075	HUWE1	CA_HPV_1	Human	Cervix	CC	3.05e-02	-4.49e-02	0.0264
10075	HUWE1	CCI_1	Human	Cervix	CC	5.39e-05	6.43e-01	0.528
10075	HUWE1	CCI_2	Human	Cervix	CC	1.97e-07	9.88e-01	0.5249
10075	HUWE1	CCI_3	Human	Cervix	CC	8.46e-04	6.21e-01	0.516
10075	HUWE1	AEH-subject1	Human	Endometrium	AEH	9.45e-10	3.77e-01	-0.3059
10075	HUWE1	AEH-subject2	Human	Endometrium	AEH	3.06e-06	2.41e-01	-0.2525
10075	HUWE1	AEH-subject3	Human	Endometrium	AEH	1.79e-06	2.69e-01	-0.2576
10075	HUWE1	AEH-subject4	Human	Endometrium	AEH	1.45e-08	3.79e-01	-0.2657
10075	HUWE1	AEH-subject5	Human	Endometrium	AEH	4.23e-04	3.97e-01	-0.2953
10075	HUWE1	EEC-subject1	Human	Endometrium	EEC	5.26e-13	4.17e-01	-0.2682
10075	HUWE1	EEC-subject3	Human	Endometrium	EEC	6.79e-10	1.91e-01	-0.2525
10075	HUWE1	EEC-subject4	Human	Endometrium	EEC	6.23e-03	2.14e-01	-0.2571
10075	HUWE1	EEC-subject5	Human	Endometrium	EEC	1.77e-07	3.24e-01	-0.249
10075	HUWE1	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	3.39e-17	1.50e-01	-0.1869
10075	HUWE1	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	4.09e-12	-4.05e-03	-0.1875
10075	HUWE1	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	3.65e-15	7.22e-02	-0.1883
10075	HUWE1	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	5.03e-08	8.68e-02	-0.1934
10075	HUWE1	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	5.71e-19	9.55e-02	-0.1917
10075	HUWE1	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	3.97e-18	1.42e-01	-0.1916
10075	HUWE1	GSM6177623_NYU_UCEC3_Vis	Human	Endometrium	EEC	3.59e-03	2.22e-01	-0.1269

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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
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:007265532	Oral cavity	NEOLP	establishment of protein localization to mitochondrion	22/2005	120/18723	8.23e-03	4.04e-02	22
GO:190492511	Oral cavity	NEOLP	positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization	5/2005	13/18723	8.62e-03	4.15e-02	5
GO:004217618	Prostate	BPH	regulation of protein catabolic process	139/3107	391/18723	3.71e-20	3.28e-17	139
GO:007259416	Prostate	BPH	establishment of protein localization to organelle	142/3107	422/18723	4.01e-18	1.31e-15	142
GO:000989618	Prostate	BPH	positive regulation of catabolic process	156/3107	492/18723	4.50e-17	1.11e-14	156
GO:001049818	Prostate	BPH	proteasomal protein catabolic process	153/3107	490/18723	4.13e-16	7.51e-14	153
GO:190332018	Prostate	BPH	regulation of protein modification by small protein conjugation or removal	90/3107	242/18723	7.37e-15	1.01e-12	90
GO:190382918	Prostate	BPH	positive regulation of cellular protein localization	98/3107	276/18723	1.46e-14	1.84e-12	98
GO:004316118	Prostate	BPH	proteasome-mediated ubiquitin-dependent protein catabolic process	127/3107	412/18723	3.84e-13	3.60e-11	127
GO:004573218	Prostate	BPH	positive regulation of protein catabolic process	82/3107	231/18723	2.08e-12	1.72e-10	82
GO:000660518	Prostate	BPH	protein targeting	102/3107	314/18723	2.51e-12	2.05e-10	102
GO:003238610	Prostate	BPH	regulation of intracellular transport	106/3107	337/18723	8.77e-12	6.70e-10	106
GO:190495117	Prostate	BPH	positive regulation of establishment of protein localization	101/3107	319/18723	1.77e-11	1.24e-09	101
GO:004851110	Prostate	BPH	rhythmic process	96/3107	298/18723	1.88e-11	1.31e-09	96
GO:003139618	Prostate	BPH	regulation of protein ubiquitination	74/3107	210/18723	3.66e-11	2.39e-09	74
GO:000762310	Prostate	BPH	circadian rhythm	73/3107	210/18723	1.02e-10	6.02e-09	73
GO:00329228	Prostate	BPH	circadian regulation of gene expression	34/3107	68/18723	2.01e-10	1.12e-08	34
GO:003315716	Prostate	BPH	regulation of intracellular protein transport	76/3107	229/18723	5.05e-10	2.56e-08	76
GO:005122217	Prostate	BPH	positive regulation of protein transport	93/3107	303/18723	6.94e-10	3.25e-08	93
GO:003238816	Prostate	BPH	positive regulation of intracellular transport	68/3107	202/18723	2.08e-09	8.35e-08	68

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0412016	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0412017	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0412023	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0412033	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa04120111	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412010	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412011	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412021	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0412031	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0412041	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0412051	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0412012	Lung	IAC	Ubiquitin mediated proteolysis	40/1053	142/8465	3.24e-07	1.76e-05	1.17e-05	40
hsa0412013	Lung	IAC	Ubiquitin mediated proteolysis	40/1053	142/8465	3.24e-07	1.76e-05	1.17e-05	40
hsa0412022	Lung	AIS	Ubiquitin mediated proteolysis	41/961	142/8465	8.01e-09	4.33e-07	2.77e-07	41
hsa0412032	Lung	AIS	Ubiquitin mediated proteolysis	41/961	142/8465	8.01e-09	4.33e-07	2.77e-07	41

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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

HUWE1

SNV

Missense_Mutation

novel

c.9365N>T

p.Ser3122Phe

p.S3122F

Q7Z6Z7

protein_coding

deleterious(0)

probably_damaging(0.974)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

HUWE1

SNV

Missense_Mutation

novel

c.2665N>A

p.Ala889Thr

p.A889T

Q7Z6Z7

protein_coding

tolerated(0.24)

benign(0.014)

TCGA-3C-AALK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

HUWE1

SNV

Missense_Mutation

c.9521N>A

p.Arg3174His

p.R3174H

Q7Z6Z7

protein_coding

deleterious(0.01)

probably_damaging(0.976)

TCGA-4H-AAAK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

HUWE1

SNV

Missense_Mutation

c.2644N>A

p.Asp882Asn

p.D882N

Q7Z6Z7

protein_coding

tolerated(0.2)

benign(0.003)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

HUWE1

SNV

Missense_Mutation

novel

c.10606N>C

p.Thr3536Pro

p.T3536P

Q7Z6Z7

protein_coding

tolerated(0.27)

benign(0.044)

TCGA-A2-A0D0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

HUWE1

SNV

Missense_Mutation

c.11357N>A

p.Arg3786Gln

p.R3786Q

Q7Z6Z7

protein_coding

tolerated(0.24)

benign(0.039)

TCGA-A2-A0ER-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

HUWE1

SNV

Missense_Mutation

c.1583N>C

p.Ile528Thr

p.I528T

Q7Z6Z7

protein_coding

deleterious(0)

possibly_damaging(0.892)

TCGA-A2-A1FW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

HUWE1

SNV

Missense_Mutation

rs782714213

c.9964N>A

p.Val3322Ile

p.V3322I

Q7Z6Z7

protein_coding

tolerated(0.39)

possibly_damaging(0.854)

TCGA-A2-A3XT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

HUWE1

SNV

Missense_Mutation

rs398124423

c.12671N>T

p.Ala4224Val

p.A4224V

Q7Z6Z7

protein_coding

tolerated(0.1)

possibly_damaging(0.688)

TCGA-A2-A3XY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HUWE1

SNV

Missense_Mutation

rs782477771

c.6008C>T

p.Thr2003Met

p.T2003M

Q7Z6Z7

protein_coding

deleterious_low_confidence(0.02)

benign(0.197)

TCGA-A7-A3J1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrazole

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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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