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: UBE2J2

Gene summary for UBE2J2

Gene summary.

Gene information	Species	Human
	Gene symbol	UBE2J2
	Gene ID	118424
	Gene name	ubiquitin conjugating enzyme E2 J2
	Gene Alias	NCUBE-2
	Cytomap	1p36.33
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	A0A024R075

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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
118424	UBE2J2	HTA11_2487_2000001011	Human	Colorectum	SER	2.20e-04	4.07e-01	-0.1808
118424	UBE2J2	HTA11_347_2000001011	Human	Colorectum	AD	2.08e-06	4.30e-01	-0.1954
118424	UBE2J2	HTA11_83_2000001011	Human	Colorectum	SER	1.86e-03	4.75e-01	-0.1526
118424	UBE2J2	HTA11_696_2000001011	Human	Colorectum	AD	2.04e-17	6.12e-01	-0.1464
118424	UBE2J2	HTA11_866_2000001011	Human	Colorectum	AD	3.82e-07	3.33e-01	-0.1001
118424	UBE2J2	HTA11_1391_2000001011	Human	Colorectum	AD	1.48e-13	6.63e-01	-0.059
118424	UBE2J2	HTA11_866_3004761011	Human	Colorectum	AD	3.62e-02	2.81e-01	0.096
118424	UBE2J2	HTA11_7696_3000711011	Human	Colorectum	AD	2.98e-10	3.45e-01	0.0674
118424	UBE2J2	HTA11_99999970781_79442	Human	Colorectum	MSS	8.45e-04	2.81e-01	0.294
118424	UBE2J2	HTA11_99999971662_82457	Human	Colorectum	MSS	4.78e-19	5.92e-01	0.3859
118424	UBE2J2	HTA11_99999974143_84620	Human	Colorectum	MSS	1.00e-04	2.14e-01	0.3005
118424	UBE2J2	A002-C-205	Human	Colorectum	FAP	1.23e-04	-1.52e-01	-0.1236
118424	UBE2J2	A018-E-020	Human	Colorectum	FAP	4.90e-03	-1.33e-01	-0.2034
118424	UBE2J2	LZE4T	Human	Esophagus	ESCC	9.07e-09	1.61e-01	0.0811
118424	UBE2J2	LZE5T	Human	Esophagus	ESCC	4.44e-02	1.42e-01	0.0514
118424	UBE2J2	LZE20T	Human	Esophagus	ESCC	1.26e-11	3.73e-01	0.0662
118424	UBE2J2	LZE22T	Human	Esophagus	ESCC	4.75e-07	3.06e-01	0.068
118424	UBE2J2	LZE24T	Human	Esophagus	ESCC	6.98e-20	5.80e-01	0.0596
118424	UBE2J2	LZE21T	Human	Esophagus	ESCC	9.88e-04	1.44e-01	0.0655
118424	UBE2J2	P1T-E	Human	Esophagus	ESCC	5.18e-13	6.28e-01	0.0875

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:00066261	Colorectum	SER	protein targeting to mitochondrion	31/2897	100/18723	7.09e-05	1.61e-03	31
GO:00069861	Colorectum	SER	response to unfolded protein	38/2897	137/18723	1.68e-04	3.16e-03	38
GO:00002091	Colorectum	SER	protein polyubiquitination	58/2897	236/18723	1.69e-04	3.18e-03	58
GO:19037471	Colorectum	SER	regulation of establishment of protein localization to mitochondrion	18/2897	50/18723	3.00e-04	4.90e-03	18
GO:19035331	Colorectum	SER	regulation of protein targeting	24/2897	81/18723	9.20e-04	1.11e-02	24
GO:19032141	Colorectum	SER	regulation of protein targeting to mitochondrion	15/2897	44/18723	1.77e-03	1.82e-02	15
GO:19037491	Colorectum	SER	positive regulation of establishment of protein localization to mitochondrion	13/2897	36/18723	1.96e-03	1.97e-02	13
GO:00365031	Colorectum	SER	ERAD pathway	28/2897	107/18723	2.92e-03	2.59e-02	28
GO:1903955	Colorectum	SER	positive regulation of protein targeting to mitochondrion	11/2897	32/18723	6.58e-03	4.68e-02	11
GO:19038292	Colorectum	MSS	positive regulation of cellular protein localization	103/3467	276/18723	1.12e-13	2.67e-11	103
GO:00104982	Colorectum	MSS	proteasomal protein catabolic process	157/3467	490/18723	2.39e-13	5.25e-11	157
GO:00725942	Colorectum	MSS	establishment of protein localization to organelle	139/3467	422/18723	5.75e-13	1.12e-10	139
GO:00068392	Colorectum	MSS	mitochondrial transport	93/3467	254/18723	6.14e-12	9.82e-10	93
GO:19049512	Colorectum	MSS	positive regulation of establishment of protein localization	110/3467	319/18723	6.30e-12	9.83e-10	110
GO:00512222	Colorectum	MSS	positive regulation of protein transport	104/3467	303/18723	3.23e-11	4.11e-09	104
GO:00431612	Colorectum	MSS	proteasome-mediated ubiquitin-dependent protein catabolic process	127/3467	412/18723	7.70e-10	6.32e-08	127
GO:00903162	Colorectum	MSS	positive regulation of intracellular protein transport	60/3467	160/18723	1.18e-08	7.08e-07	60
GO:00323882	Colorectum	MSS	positive regulation of intracellular transport	70/3467	202/18723	3.32e-08	1.82e-06	70
GO:00066052	Colorectum	MSS	protein targeting	97/3467	314/18723	6.76e-08	3.46e-06	97
GO:00331572	Colorectum	MSS	regulation of intracellular protein transport	76/3467	229/18723	7.03e-08	3.56e-06	76

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05012	Colorectum	AD	Parkinson disease	147/2092	266/8465	2.53e-27	8.48e-25	5.41e-25	147
hsa05022	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa050121	Colorectum	AD	Parkinson disease	147/2092	266/8465	2.53e-27	8.48e-25	5.41e-25	147
hsa050221	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa050122	Colorectum	SER	Parkinson disease	132/1580	266/8465	2.72e-31	9.03e-29	6.55e-29	132
hsa050222	Colorectum	SER	Pathways of neurodegeneration - multiple diseases	168/1580	476/8465	6.23e-19	2.07e-17	1.50e-17	168
hsa041412	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa050123	Colorectum	SER	Parkinson disease	132/1580	266/8465	2.72e-31	9.03e-29	6.55e-29	132
hsa050223	Colorectum	SER	Pathways of neurodegeneration - multiple diseases	168/1580	476/8465	6.23e-19	2.07e-17	1.50e-17	168
hsa041413	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa050124	Colorectum	MSS	Parkinson disease	140/1875	266/8465	2.32e-28	7.79e-26	4.77e-26	140
hsa050224	Colorectum	MSS	Pathways of neurodegeneration - multiple diseases	192/1875	476/8465	2.79e-20	1.04e-18	6.36e-19	192
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55

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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

UBE2J2

SNV

Missense_Mutation

c.785N>T

p.Ala262Val

p.A262V

Q8N2K1

protein_coding

deleterious(0.03)

probably_damaging(0.998)

TCGA-A2-A04P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol

UBE2J2

SNV

Missense_Mutation

c.689N>A

p.Pro230Gln

p.P230Q

Q8N2K1

protein_coding

tolerated(0.28)

benign(0.189)

TCGA-C8-A274-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

UBE2J2

insertion

In_Frame_Ins

novel

c.191_192insACTCAGGAGGCTGAGGCAGGAGAATCGCTTGAA

p.Val64_Arg65insLeuArgArgLeuArgGlnGluAsnArgLeuAsn

p.V64_R65insLRRLRQENRLN

Q8N2K1

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

UBE2J2

deletion

Frame_Shift_Del

novel

c.670delC

p.His224MetfsTer31

p.H224Mfs*31

Q8N2K1

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

UBE2J2

SNV

Missense_Mutation

rs146718362

c.581G>A

p.Ser194Asn

p.S194N

Q8N2K1

protein_coding

tolerated(0.3)

benign(0)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

UBE2J2

SNV

Missense_Mutation

c.83C>T

p.Pro28Leu

p.P28L

Q8N2K1

protein_coding

deleterious(0.03)

probably_damaging(0.934)

TCGA-IR-A3LL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

UBE2J2

insertion

Frame_Shift_Ins

novel

c.348_349insATCGCAGGGGCTCTGGACCCCAGCTGCCCACAGTT

p.His117IlefsTer27

p.H117Ifs*27

Q8N2K1

protein_coding

TCGA-IR-A3LB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

UBE2J2

SNV

Missense_Mutation

c.610N>T

p.Asp204Tyr

p.D204Y

Q8N2K1

protein_coding

deleterious(0)

possibly_damaging(0.659)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

UBE2J2

SNV

Missense_Mutation

c.364A>G

p.Asn122Asp

p.N122D

Q8N2K1

protein_coding

deleterious(0.02)

benign(0.378)

TCGA-AA-A02R-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

UBE2J2

SNV

Missense_Mutation

c.287N>C

p.Met96Thr

p.M96T

Q8N2K1

protein_coding

tolerated(0.05)

benign(0.248)

TCGA-D5-6540-01

Colorectum

colon adenocarcinoma

Male

>=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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