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: UBE3C

Gene summary for UBE3C

Gene summary.

Gene information	Species	Human
	Gene symbol	UBE3C
	Gene ID	9690
	Gene name	ubiquitin protein ligase E3C
	Gene Alias	HECTH2
	Cytomap	7q36.3
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	Q15386

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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
9690	UBE3C	CCI_2	Human	Cervix	CC	2.22e-18	1.64e+00	0.5249
9690	UBE3C	CCI_3	Human	Cervix	CC	1.60e-11	8.67e-01	0.516
9690	UBE3C	HTA11_3410_2000001011	Human	Colorectum	AD	2.49e-07	-4.41e-01	0.0155
9690	UBE3C	HTA11_347_2000001011	Human	Colorectum	AD	1.09e-06	4.80e-01	-0.1954
9690	UBE3C	HTA11_99999965062_69753	Human	Colorectum	MSI-H	8.62e-03	7.57e-01	0.3487
9690	UBE3C	HTA11_99999965104_69814	Human	Colorectum	MSS	1.18e-04	5.59e-01	0.281
9690	UBE3C	A001-C-207	Human	Colorectum	FAP	1.06e-04	-2.89e-01	0.1278
9690	UBE3C	A015-C-203	Human	Colorectum	FAP	5.53e-39	-5.71e-01	-0.1294
9690	UBE3C	A015-C-204	Human	Colorectum	FAP	7.47e-07	-2.35e-01	-0.0228
9690	UBE3C	A014-C-040	Human	Colorectum	FAP	5.01e-06	-4.52e-01	-0.1184
9690	UBE3C	A002-C-201	Human	Colorectum	FAP	6.21e-23	-5.88e-01	0.0324
9690	UBE3C	A001-C-119	Human	Colorectum	FAP	3.56e-09	-4.10e-01	-0.1557
9690	UBE3C	A001-C-108	Human	Colorectum	FAP	9.26e-21	-3.91e-01	-0.0272
9690	UBE3C	A002-C-205	Human	Colorectum	FAP	1.25e-29	-4.72e-01	-0.1236
9690	UBE3C	A001-C-104	Human	Colorectum	FAP	7.32e-04	-2.05e-01	0.0184
9690	UBE3C	A015-C-005	Human	Colorectum	FAP	3.26e-06	-3.47e-01	-0.0336
9690	UBE3C	A015-C-006	Human	Colorectum	FAP	1.07e-17	-4.14e-01	-0.0994
9690	UBE3C	A015-C-106	Human	Colorectum	FAP	1.14e-15	-3.95e-01	-0.0511
9690	UBE3C	A002-C-114	Human	Colorectum	FAP	5.39e-27	-5.69e-01	-0.1561
9690	UBE3C	A015-C-104	Human	Colorectum	FAP	2.08e-35	-4.75e-01	-0.1899

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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
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:00002097	Cervix	CC	protein polyubiquitination	58/2311	236/18723	1.57e-07	7.41e-06	58
GO:0000209	Colorectum	AD	protein polyubiquitination	78/3918	236/18723	8.71e-06	2.06e-04	78
GO:00002092	Colorectum	MSS	protein polyubiquitination	72/3467	236/18723	5.19e-06	1.42e-04	72
GO:00002093	Colorectum	FAP	protein polyubiquitination	59/2622	236/18723	4.53e-06	1.52e-04	59
GO:00002094	Colorectum	CRC	protein polyubiquitination	46/2078	236/18723	9.91e-05	1.98e-03	46
GO:000020917	Esophagus	ESCC	protein polyubiquitination	170/8552	236/18723	1.40e-16	1.09e-14	170
GO:00002095	Liver	NAFLD	protein polyubiquitination	51/1882	236/18723	1.04e-07	8.10e-06	51
GO:000020921	Liver	HCC	protein polyubiquitination	151/7958	236/18723	1.90e-11	7.59e-10	151
GO:00002096	Lung	IAC	protein polyubiquitination	49/2061	236/18723	8.51e-06	2.89e-04	49
GO:000020912	Lung	AIS	protein polyubiquitination	49/1849	236/18723	3.85e-07	3.16e-05	49
GO:000020910	Oral cavity	OSCC	protein polyubiquitination	150/7305	236/18723	1.59e-14	9.27e-13	150
GO:000020923	Oral cavity	EOLP	protein polyubiquitination	62/2218	236/18723	7.88e-10	5.90e-08	62
GO:000020931	Oral cavity	NEOLP	protein polyubiquitination	53/2005	236/18723	1.22e-07	4.38e-06	53
GO:00002099	Prostate	BPH	protein polyubiquitination	64/3107	236/18723	2.83e-05	3.31e-04	64
GO:000020914	Prostate	Tumor	protein polyubiquitination	64/3246	236/18723	1.08e-04	1.03e-03	64
GO:000020918	Skin	AK	protein polyubiquitination	41/1910	236/18723	4.78e-04	4.44e-03	41
GO:000020919	Skin	SCCIS	protein polyubiquitination	22/919	236/18723	3.03e-03	2.76e-02	22
GO:000020924	Skin	cSCC	protein polyubiquitination	103/4864	236/18723	2.57e-09	9.09e-08	103
GO:000020920	Thyroid	PTC	protein polyubiquitination	128/5968	236/18723	7.81e-13	3.65e-11	128
GO:0000209110	Thyroid	ATC	protein polyubiquitination	134/6293	236/18723	1.86e-13	9.20e-12	134

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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
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041206	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041207	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041208	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa041209	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
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
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

UBE3C

SNV

Missense_Mutation

novel

c.3113N>A

p.Gly1038Glu

p.G1038E

Q15386

protein_coding

deleterious(0)

probably_damaging(0.94)

TCGA-5L-AAT0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

UBE3C

SNV

Missense_Mutation

c.2560G>A

p.Val854Met

p.V854M

Q15386

protein_coding

deleterious(0)

probably_damaging(0.946)

TCGA-A8-A09W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

UBE3C

SNV

Missense_Mutation

novel

c.2650G>C

p.Gly884Arg

p.G884R

Q15386

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-AC-A3W5-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

UBE3C

SNV

Missense_Mutation

novel

c.2468N>C

p.Arg823Thr

p.R823T

Q15386

protein_coding

deleterious(0.01)

possibly_damaging(0.903)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

UBE3C

SNV

Missense_Mutation

c.92G>A

p.Arg31His

p.R31H

Q15386

protein_coding

tolerated(0.25)

benign(0.074)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBE3C

SNV

Missense_Mutation

novel

c.509G>A

p.Arg170Lys

p.R170K

Q15386

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBE3C

SNV

Missense_Mutation

c.1885N>C

p.Ser629Pro

p.S629P

Q15386

protein_coding

deleterious(0)

probably_damaging(0.949)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UBE3C

SNV

Missense_Mutation

c.2081N>T

p.Pro694Leu

p.P694L

Q15386

protein_coding

deleterious(0.01)

possibly_damaging(0.796)

TCGA-BH-A18Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UBE3C

insertion

In_Frame_Ins

novel

c.2395_2396insCGCATTCAAAGCCATCCCGAGCCACATCGGCCTGTGGGCTGCAGG

p.Leu799delinsProHisSerLysProSerArgAlaThrSerAlaCysGlyLeuGlnVal

p.L799delinsPHSKPSRATSACGLQV

Q15386

protein_coding

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

UBE3C

insertion

Frame_Shift_Ins

novel

c.3016_3017insGGTGTTATTTCTGT

p.Glu1006GlyfsTer12

p.E1006Gfs*12

Q15386

protein_coding

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

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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