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: JUN

Gene summary for JUN

Gene summary.

Gene information	Species	Human
	Gene symbol	JUN
	Gene ID	3725
	Gene name	Jun proto-oncogene, AP-1 transcription factor subunit
	Gene Alias	AP-1
	Cytomap	1p32.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	P05412

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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
3725	JUN	GSM4909277	Human	Breast	Precancer	7.18e-03	5.72e-01	0.0177
3725	JUN	GSM4909280	Human	Breast	Precancer	2.42e-04	4.64e-01	0.0305
3725	JUN	GSM4909281	Human	Breast	IDC	3.67e-06	-3.81e-01	0.21
3725	JUN	GSM4909286	Human	Breast	IDC	5.17e-21	-5.96e-01	0.1081
3725	JUN	GSM4909290	Human	Breast	IDC	3.50e-16	-7.48e-01	0.2096
3725	JUN	GSM4909294	Human	Breast	IDC	1.12e-18	-5.17e-01	0.2022
3725	JUN	GSM4909296	Human	Breast	IDC	9.17e-04	-2.38e-01	0.1524
3725	JUN	GSM4909297	Human	Breast	IDC	2.57e-19	2.40e-01	0.1517
3725	JUN	GSM4909299	Human	Breast	IDC	7.60e-13	3.53e-01	0.035
3725	JUN	GSM4909300	Human	Breast	IDC	1.92e-05	3.85e-01	0.0334
3725	JUN	GSM4909301	Human	Breast	IDC	1.41e-02	1.86e-01	0.1577
3725	JUN	GSM4909304	Human	Breast	IDC	9.85e-05	-3.51e-01	0.1636
3725	JUN	GSM4909305	Human	Breast	IDC	3.00e-12	3.98e-01	0.0436
3725	JUN	GSM4909307	Human	Breast	IDC	2.30e-07	-4.23e-01	0.1569
3725	JUN	GSM4909311	Human	Breast	IDC	2.02e-23	-1.01e-01	0.1534
3725	JUN	GSM4909312	Human	Breast	IDC	3.80e-20	4.05e-01	0.1552
3725	JUN	GSM4909315	Human	Breast	IDC	4.47e-14	-4.67e-01	0.21
3725	JUN	GSM4909316	Human	Breast	IDC	7.19e-11	-8.51e-01	0.21
3725	JUN	GSM4909317	Human	Breast	IDC	6.03e-12	3.80e-01	0.1355
3725	JUN	GSM4909319	Human	Breast	IDC	1.13e-32	5.91e-02	0.1563

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00069799	Breast	Precancer	response to oxidative stress	70/1080	446/18723	1.59e-14	4.26e-12	70
GO:00621979	Breast	Precancer	cellular response to chemical stress	51/1080	337/18723	2.40e-10	2.34e-08	51
GO:00160329	Breast	Precancer	viral process	58/1080	415/18723	3.42e-10	3.16e-08	58
GO:00003029	Breast	Precancer	response to reactive oxygen species	38/1080	222/18723	1.47e-09	1.23e-07	38
GO:00709979	Breast	Precancer	neuron death	50/1080	361/18723	7.75e-09	5.70e-07	50
GO:00514029	Breast	Precancer	neuron apoptotic process	38/1080	246/18723	2.68e-08	1.75e-06	38
GO:00345999	Breast	Precancer	cellular response to oxidative stress	42/1080	288/18723	2.78e-08	1.79e-06	42
GO:00444039	Breast	Precancer	biological process involved in symbiotic interaction	42/1080	290/18723	3.40e-08	2.11e-06	42
GO:00086378	Breast	Precancer	apoptotic mitochondrial changes	23/1080	107/18723	3.44e-08	2.12e-06	23
GO:00349769	Breast	Precancer	response to endoplasmic reticulum stress	38/1080	256/18723	7.89e-08	4.60e-06	38
GO:00425429	Breast	Precancer	response to hydrogen peroxide	26/1080	146/18723	2.52e-07	1.26e-05	26
GO:00100389	Breast	Precancer	response to metal ion	47/1080	373/18723	3.88e-07	1.79e-05	47
GO:00511019	Breast	Precancer	regulation of DNA binding	22/1080	118/18723	9.28e-07	3.71e-05	22
GO:19012149	Breast	Precancer	regulation of neuron death	41/1080	319/18723	1.27e-06	4.80e-05	41
GO:00435237	Breast	Precancer	regulation of neuron apoptotic process	31/1080	212/18723	1.69e-06	6.08e-05	31
GO:00075653	Breast	Precancer	female pregnancy	29/1080	193/18723	2.07e-06	7.31e-05	29
GO:00510989	Breast	Precancer	regulation of binding	44/1080	363/18723	2.59e-06	8.65e-05	44
GO:00447063	Breast	Precancer	multi-multicellular organism process	31/1080	220/18723	3.73e-06	1.19e-04	31
GO:00300999	Breast	Precancer	myeloid cell differentiation	45/1080	381/18723	4.00e-06	1.25e-04	45
GO:00018367	Breast	Precancer	release of cytochrome c from mitochondria	14/1080	59/18723	4.80e-06	1.47e-04	14

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0493216	Breast	Precancer	Non-alcoholic fatty liver disease	48/684	155/8465	6.16e-17	1.50e-15	1.15e-15	48
hsa0513218	Breast	Precancer	Salmonella infection	49/684	249/8465	2.92e-09	6.15e-08	4.71e-08	49
hsa0513018	Breast	Precancer	Pathogenic Escherichia coli infection	38/684	197/8465	3.12e-07	5.81e-06	4.45e-06	38
hsa0513118	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0516718	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0491518	Breast	Precancer	Estrogen signaling pathway	28/684	138/8465	4.10e-06	5.39e-05	4.13e-05	28
hsa0541818	Breast	Precancer	Fluid shear stress and atherosclerosis	28/684	139/8465	4.74e-06	6.00e-05	4.59e-05	28
hsa0541718	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0516918	Breast	Precancer	Epstein-Barr virus infection	35/684	202/8465	1.15e-05	1.26e-04	9.64e-05	35
hsa0465716	Breast	Precancer	IL-17 signaling pathway	20/684	94/8465	4.74e-05	4.54e-04	3.48e-04	20
hsa042108	Breast	Precancer	Apoptosis	25/684	136/8465	7.61e-05	6.87e-04	5.26e-04	25
hsa0516618	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0413716	Breast	Precancer	Mitophagy - animal	15/684	72/8465	5.22e-04	3.93e-03	3.01e-03	15
hsa05031	Breast	Precancer	Amphetamine addiction	14/684	69/8465	1.05e-03	7.35e-03	5.63e-03	14
hsa052036	Breast	Precancer	Viral carcinogenesis	27/684	204/8465	7.19e-03	4.06e-02	3.11e-02	27
hsa0493217	Breast	Precancer	Non-alcoholic fatty liver disease	48/684	155/8465	6.16e-17	1.50e-15	1.15e-15	48
hsa0513219	Breast	Precancer	Salmonella infection	49/684	249/8465	2.92e-09	6.15e-08	4.71e-08	49
hsa0513019	Breast	Precancer	Pathogenic Escherichia coli infection	38/684	197/8465	3.12e-07	5.81e-06	4.45e-06	38
hsa0513119	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0516719	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
JUN	MLUM	Breast	DCIS	DUSP1,JUNB,MALAT1, etc.	6.42e-01
JUN	CD4TN	Cervix	CC	HSPA1B,DNAJB1,HSPA1A, etc.	1.26e-01
JUN	CD8TEFF	Cervix	CC	HSPA1B,DNAJB1,HSPA1A, etc.	8.34e-02
JUN	TFH	Cervix	CC	HSPA1B,DNAJB1,HSPA1A, etc.	6.17e-02
JUN	CD8TEXP	Liver	Cirrhotic	HSPA1A,HSPA1B,HSPB1, etc.	1.35e-01
JUN	CD8TCM	Pancreas	PDAC	DNAJB1,HSPA1B,ID2, etc.	2.45e-01

∗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

JUN

SNV

Missense_Mutation

c.334G>A

p.Glu112Lys

p.E112K

P05412

protein_coding

deleterious(0.01)

probably_damaging(0.959)

TCGA-D8-A1JJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

JUN

insertion

In_Frame_Ins

novel

c.862_863insGGGGCAACG

p.Lys288delinsArgGlyAsnGlu

p.K288delinsRGNE

P05412

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

JUN

SNV

Missense_Mutation

novel

c.659N>G

p.Pro220Arg

p.P220R

P05412

protein_coding

deleterious(0)

probably_damaging(0.977)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

JUN

SNV

Missense_Mutation

c.635N>T

p.Pro212Leu

p.P212L

P05412

protein_coding

tolerated(0.3)

benign(0.096)

TCGA-A6-5657-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Ancillary

leucovorin

JUN

SNV

Missense_Mutation

c.350N>A

p.Ala117Asp

p.A117D

P05412

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-AA-3811-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

JUN

SNV

Missense_Mutation

novel

c.788G>A

p.Arg263His

p.R263H

P05412

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

JUN

insertion

Frame_Shift_Ins

novel

c.769dupA

p.Arg257LysfsTer53

p.R257Kfs*53

P05412

protein_coding

TCGA-CM-6172-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Ancillary

leucovorin

JUN

insertion

Frame_Shift_Ins

novel

c.198_199insT

p.Gly67TrpfsTer40

p.G67Wfs*40

P05412

protein_coding

TCGA-D5-6928-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

JUN

SNV

Missense_Mutation

c.870N>T

p.Gln290His

p.Q290H

P05412

protein_coding

deleterious(0.02)

possibly_damaging(0.599)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

JUN

SNV

Missense_Mutation

novel

c.296N>A

p.Cys99Tyr

p.C99Y

P05412

protein_coding

tolerated(1)

benign(0.012)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

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
3725	JUN	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TUMOR SUPPRESSOR, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		DIPHENHYDRAMINE HYDROCHLORIDE	DIPHENHYDRAMINE HYDROCHLORIDE
3725	JUN	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TUMOR SUPPRESSOR, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		COLCHICINE	COLCHICINE
3725	JUN	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TUMOR SUPPRESSOR, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		CIPROFIBRATE	CIPROFIBRATE	16680159
3725	JUN	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TUMOR SUPPRESSOR, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		VINBLASTINE SULFATE	VINBLASTINE SULFATE
3725	JUN	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TUMOR SUPPRESSOR, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		PATULIN	PATULIN	16680159
3725	JUN	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TUMOR SUPPRESSOR, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		ALPHA-DIFLUOROMETHYLORNITHINE		9950818
3725	JUN	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TUMOR SUPPRESSOR, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		METHIMAZOLE	METHIMAZOLE
3725	JUN	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TUMOR SUPPRESSOR, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		DFMO		9950818
3725	JUN	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TUMOR SUPPRESSOR, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		2-MERCAPTOPYRIMIDINE	2-MERCAPTOPYRIMIDINE
3725	JUN	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TUMOR SUPPRESSOR, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		SODIUM SELENITE	SODIUM SELENITE

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