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: UBE2N

Gene summary for UBE2N

Gene summary.

Gene information	Species	Human
	Gene symbol	UBE2N
	Gene ID	7334
	Gene name	ubiquitin conjugating enzyme E2 N
	Gene Alias	HEL-S-71
	Cytomap	12q22
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	P61088

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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
7334	UBE2N	AEH-subject2	Human	Endometrium	AEH	8.15e-07	-2.90e-01	-0.2525
7334	UBE2N	AEH-subject3	Human	Endometrium	AEH	5.40e-05	-2.84e-01	-0.2576
7334	UBE2N	AEH-subject4	Human	Endometrium	AEH	3.22e-04	-3.20e-01	-0.2657
7334	UBE2N	EEC-subject1	Human	Endometrium	EEC	7.67e-04	-2.13e-01	-0.2682
7334	UBE2N	EEC-subject2	Human	Endometrium	EEC	1.27e-08	-3.59e-01	-0.2607
7334	UBE2N	EEC-subject3	Human	Endometrium	EEC	5.48e-17	-2.95e-01	-0.2525
7334	UBE2N	GSM5276934	Human	Endometrium	EEC	1.18e-10	2.65e-01	-0.0913
7334	UBE2N	GSM5276937	Human	Endometrium	EEC	2.01e-12	4.08e-01	-0.0897
7334	UBE2N	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	3.63e-22	-2.41e-01	-0.1869
7334	UBE2N	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	1.50e-22	-2.34e-01	-0.1875
7334	UBE2N	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	1.47e-26	-2.96e-01	-0.1883
7334	UBE2N	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	3.07e-23	-2.87e-01	-0.1934
7334	UBE2N	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	2.01e-36	-2.04e-01	-0.1917
7334	UBE2N	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	5.59e-42	-1.73e-01	-0.1916
7334	UBE2N	LZE4T	Human	Esophagus	ESCC	8.46e-13	4.33e-01	0.0811
7334	UBE2N	LZE7T	Human	Esophagus	ESCC	3.95e-10	1.20e+00	0.0667
7334	UBE2N	LZE8T	Human	Esophagus	ESCC	3.64e-10	6.75e-01	0.067
7334	UBE2N	LZE20T	Human	Esophagus	ESCC	2.02e-03	1.22e-01	0.0662
7334	UBE2N	LZE24T	Human	Esophagus	ESCC	4.79e-16	8.53e-01	0.0596
7334	UBE2N	LZE21T	Human	Esophagus	ESCC	1.10e-02	3.62e-01	0.0655

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:190332016	Endometrium	AEH	regulation of protein modification by small protein conjugation or removal	67/2100	242/18723	1.10e-12	2.26e-10	67
GO:003139616	Endometrium	AEH	regulation of protein ubiquitination	57/2100	210/18723	1.24e-10	1.40e-08	57
GO:00431229	Endometrium	AEH	regulation of I-kappaB kinase/NF-kappaB signaling	52/2100	249/18723	6.58e-06	1.59e-04	52
GO:00431238	Endometrium	AEH	positive regulation of I-kappaB kinase/NF-kappaB signaling	41/2100	186/18723	1.59e-05	3.32e-04	41
GO:00072498	Endometrium	AEH	I-kappaB kinase/NF-kappaB signaling	55/2100	281/18723	2.60e-05	4.88e-04	55
GO:19033225	Endometrium	AEH	positive regulation of protein modification by small protein conjugation or removal	31/2100	138/18723	1.14e-04	1.61e-03	31
GO:00313984	Endometrium	AEH	positive regulation of protein ubiquitination	27/2100	119/18723	2.57e-04	3.04e-03	27
GO:00002098	Endometrium	AEH	protein polyubiquitination	44/2100	236/18723	4.83e-04	4.97e-03	44
GO:00514388	Endometrium	AEH	regulation of ubiquitin-protein transferase activity	15/2100	53/18723	5.25e-04	5.31e-03	15
GO:00027645	Endometrium	AEH	immune response-regulating signaling pathway	76/2100	468/18723	5.76e-04	5.71e-03	76
GO:00508525	Endometrium	AEH	T cell receptor signaling pathway	26/2100	123/18723	1.03e-03	9.15e-03	26
GO:200102010	Endometrium	AEH	regulation of response to DNA damage stimulus	40/2100	219/18723	1.28e-03	1.09e-02	40
GO:00510905	Endometrium	AEH	regulation of DNA-binding transcription factor activity	69/2100	440/18723	2.51e-03	1.87e-02	69
GO:00510549	Endometrium	AEH	positive regulation of DNA metabolic process	36/2100	201/18723	3.05e-03	2.16e-02	36
GO:190332017	Endometrium	EEC	regulation of protein modification by small protein conjugation or removal	72/2168	242/18723	1.45e-14	4.36e-12	72
GO:003139617	Endometrium	EEC	regulation of protein ubiquitination	62/2168	210/18723	1.42e-12	2.76e-10	62
GO:004312216	Endometrium	EEC	regulation of I-kappaB kinase/NF-kappaB signaling	53/2168	249/18723	7.59e-06	1.73e-04	53
GO:004312314	Endometrium	EEC	positive regulation of I-kappaB kinase/NF-kappaB signaling	42/2168	186/18723	1.47e-05	2.87e-04	42
GO:000724915	Endometrium	EEC	I-kappaB kinase/NF-kappaB signaling	57/2168	281/18723	1.60e-05	3.12e-04	57
GO:190332213	Endometrium	EEC	positive regulation of protein modification by small protein conjugation or removal	33/2168	138/18723	3.49e-05	5.90e-04	33

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513126	Endometrium	AEH	Shigellosis	78/1197	247/8465	9.23e-13	2.00e-11	1.46e-11	78
hsa0412016	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa05131111	Endometrium	AEH	Shigellosis	78/1197	247/8465	9.23e-13	2.00e-11	1.46e-11	78
hsa0412017	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0513127	Endometrium	EEC	Shigellosis	79/1237	247/8465	1.80e-12	3.95e-11	2.95e-11	79
hsa0412023	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0513136	Endometrium	EEC	Shigellosis	79/1237	247/8465	1.80e-12	3.95e-11	2.95e-11	79
hsa0412033	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa05131310	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa0412021	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0513122	Liver	Cirrhotic	Shigellosis	105/2530	247/8465	1.31e-05	1.21e-04	7.48e-05	105
hsa0412031	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0513132	Liver	Cirrhotic	Shigellosis	105/2530	247/8465	1.31e-05	1.21e-04	7.48e-05	105
hsa0412041	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0513142	Liver	HCC	Shigellosis	150/4020	247/8465	1.53e-05	1.04e-04	5.81e-05	150
hsa0412051	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0513152	Liver	HCC	Shigellosis	150/4020	247/8465	1.53e-05	1.04e-04	5.81e-05	150

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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

UBE2N

SNV

Missense_Mutation

novel

c.65N>A

p.Gly22Asp

p.G22D

P61088

protein_coding

deleterious(0.03)

benign(0.303)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

UBE2N

SNV

Missense_Mutation

novel

c.434N>T

p.Arg145Met

p.R145M

P61088

protein_coding

deleterious(0.01)

benign(0.014)

TCGA-AM-5820-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

UBE2N

SNV

Missense_Mutation

c.193G>A

p.Ala65Thr

p.A65T

P61088

protein_coding

tolerated(0.19)

benign(0.012)

TCGA-G4-6628-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

UBE2N

SNV

Missense_Mutation

c.416C>T

p.Thr139Ile

p.T139I

P61088

protein_coding

tolerated(0.07)

benign(0.159)

TCGA-A5-A0VQ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

UBE2N

SNV

Missense_Mutation

novel

c.61N>T

p.Pro21Ser

p.P21S

P61088

protein_coding

tolerated(0.08)

benign(0.125)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UBE2N

SNV

Missense_Mutation

c.93N>A

p.Asn31Lys

p.N31K

P61088

protein_coding

deleterious(0.01)

probably_damaging(0.976)

TCGA-B5-A0JT-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Hormone Therapy

megace

UBE2N

SNV

Missense_Mutation

c.225T>G

p.Ile75Met

p.I75M

P61088

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-BK-A6W3-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UBE2N

SNV

Missense_Mutation

c.71N>G

p.Lys24Arg

p.K24R

P61088

protein_coding

tolerated(0.09)

benign(0.062)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UBE2N

SNV

Missense_Mutation

novel

c.5N>T

p.Ala2Val

p.A2V

P61088

protein_coding

deleterious_low_confidence(0.01)

benign(0.012)

TCGA-DI-A1NO-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

UBE2N

SNV

Missense_Mutation

novel

c.424G>T

p.Ala142Ser

p.A142S

P61088

protein_coding

tolerated(0.2)

benign(0.019)

TCGA-EO-A3AV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

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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
7334	UBE2N	ENZYME, DRUGGABLE GENOME		NSC-60340	CHEMBL1534034
7334	UBE2N	ENZYME, DRUGGABLE GENOME		THONZONIUM BROMIDE	THONZONIUM BROMIDE
7334	UBE2N	ENZYME, DRUGGABLE GENOME		AMINODIMETHOXYQUINAZOLINYLPIPERAZINE	AMINODIMETHOXYQUINAZOLINYLPIPERAZINE
7334	UBE2N	ENZYME, DRUGGABLE GENOME		SPHINGOSINE	SPHINGOSINE
7334	UBE2N	ENZYME, DRUGGABLE GENOME		CHLORHEXIDINE	CHLORHEXIDINE
7334	UBE2N	ENZYME, DRUGGABLE GENOME		HYDROXYSTILBAMIDINE ISETHIONATE	HYDROXYSTILBAMIDINE ISETHIONATE
7334	UBE2N	ENZYME, DRUGGABLE GENOME		ALEXIDINE HYDROCHLORIDE	ALEXIDINE HYDROCHLORIDE
7334	UBE2N	ENZYME, DRUGGABLE GENOME		GNF-PF-3286	CHEMBL581880
7334	UBE2N	ENZYME, DRUGGABLE GENOME		TCMDC-124022	CHEMBL548017
7334	UBE2N	ENZYME, DRUGGABLE GENOME		RALOXIFENE HYDROCHLORIDE	RALOXIFENE HYDROCHLORIDE

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