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:00065135	Oral cavity	OSCC	protein monoubiquitination	47/7305	67/18723	2.32e-07	3.68e-06	47
GO:00070307	Oral cavity	OSCC	Golgi organization	92/7305	157/18723	4.96e-07	7.27e-06	92
GO:004851116	Oral cavity	OSCC	rhythmic process	157/7305	298/18723	1.00e-06	1.36e-05	157
GO:00482843	Oral cavity	OSCC	organelle fusion	82/7305	141/18723	3.08e-06	3.72e-05	82
GO:19037478	Oral cavity	OSCC	regulation of establishment of protein localization to mitochondrion	35/7305	50/18723	8.76e-06	9.31e-05	35
GO:19035337	Oral cavity	OSCC	regulation of protein targeting	51/7305	81/18723	1.08e-05	1.13e-04	51
GO:19037497	Oral cavity	OSCC	positive regulation of establishment of protein localization to mitochondrion	27/7305	36/18723	1.24e-05	1.26e-04	27
GO:00619127	Oral cavity	OSCC	selective autophagy	44/7305	68/18723	1.57e-05	1.57e-04	44
GO:00108239	Oral cavity	OSCC	negative regulation of mitochondrion organization	34/7305	49/18723	1.59e-05	1.59e-04	34
GO:000762316	Oral cavity	OSCC	circadian rhythm	110/7305	210/18723	5.40e-05	4.48e-04	110
GO:19032147	Oral cavity	OSCC	regulation of protein targeting to mitochondrion	30/7305	44/18723	8.41e-05	6.44e-04	30
GO:19039555	Oral cavity	OSCC	positive regulation of protein targeting to mitochondrion	23/7305	32/18723	1.67e-04	1.14e-03	23
GO:00062842	Oral cavity	OSCC	base-excision repair	28/7305	43/18723	4.71e-04	2.79e-03	28
GO:00329229	Oral cavity	OSCC	circadian regulation of gene expression	40/7305	68/18723	7.28e-04	3.98e-03	40
GO:00610253	Oral cavity	OSCC	membrane fusion	84/7305	163/18723	7.56e-04	4.12e-03	84
GO:00004238	Oral cavity	OSCC	mitophagy	19/7305	28/18723	1.88e-03	8.84e-03	19
GO:00987805	Oral cavity	OSCC	response to mitochondrial depolarisation	14/7305	19/18723	2.31e-03	1.02e-02	14
GO:19049232	Oral cavity	OSCC	regulation of autophagy of mitochondrion in response to mitochondrial depolarization	11/7305	14/18723	3.09e-03	1.33e-02	11
GO:00080531	Oral cavity	OSCC	mitochondrial fusion	18/7305	27/18723	3.34e-03	1.42e-02	18
GO:19049253	Oral cavity	OSCC	positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization	10/7305	13/18723	6.32e-03	2.35e-02	10

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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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