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: EGR1

Gene summary for EGR1

Gene summary.

Gene information	Species	Human
	Gene symbol	EGR1
	Gene ID	1958
	Gene name	early growth response 1
	Gene Alias	AT225
	Cytomap	5q31.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P18146

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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
1958	EGR1	GSM4909282	Human	Breast	IDC	1.75e-31	6.52e-01	-0.0288
1958	EGR1	GSM4909285	Human	Breast	IDC	2.97e-06	-1.52e-01	0.21
1958	EGR1	GSM4909286	Human	Breast	IDC	1.17e-24	4.18e-01	0.1081
1958	EGR1	GSM4909290	Human	Breast	IDC	7.72e-06	-5.19e-01	0.2096
1958	EGR1	GSM4909293	Human	Breast	IDC	5.19e-15	5.65e-01	0.1581
1958	EGR1	GSM4909297	Human	Breast	IDC	2.08e-12	5.12e-01	0.1517
1958	EGR1	GSM4909298	Human	Breast	IDC	3.77e-05	3.93e-01	0.1551
1958	EGR1	GSM4909299	Human	Breast	IDC	8.42e-53	1.02e+00	0.035
1958	EGR1	GSM4909300	Human	Breast	IDC	2.23e-04	5.74e-01	0.0334
1958	EGR1	GSM4909301	Human	Breast	IDC	4.12e-22	6.00e-01	0.1577
1958	EGR1	GSM4909303	Human	Breast	IDC	3.80e-03	6.25e-01	0.0438
1958	EGR1	GSM4909305	Human	Breast	IDC	3.22e-07	3.56e-01	0.0436
1958	EGR1	GSM4909306	Human	Breast	IDC	9.85e-03	3.47e-02	0.1564
1958	EGR1	GSM4909308	Human	Breast	IDC	1.00e-25	6.80e-01	0.158
1958	EGR1	GSM4909309	Human	Breast	IDC	6.60e-07	5.27e-01	0.0483
1958	EGR1	GSM4909311	Human	Breast	IDC	6.69e-09	-1.54e-03	0.1534
1958	EGR1	GSM4909312	Human	Breast	IDC	1.78e-09	5.00e-01	0.1552
1958	EGR1	GSM4909313	Human	Breast	IDC	4.90e-23	7.96e-01	0.0391
1958	EGR1	GSM4909316	Human	Breast	IDC	1.70e-05	-6.92e-01	0.21
1958	EGR1	GSM4909317	Human	Breast	IDC	2.34e-09	4.30e-01	0.1355

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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
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:003011110	Oral cavity	OSCC	regulation of Wnt signaling pathway	165/7305	328/18723	1.87e-05	1.80e-04	165
GO:00714569	Oral cavity	OSCC	cellular response to hypoxia	84/7305	151/18723	2.46e-05	2.30e-04	84
GO:003629417	Oral cavity	OSCC	cellular response to decreased oxygen levels	88/7305	161/18723	3.91e-05	3.43e-04	88
GO:00421804	Oral cavity	OSCC	cellular ketone metabolic process	111/7305	211/18723	3.94e-05	3.45e-04	111
GO:000762316	Oral cavity	OSCC	circadian rhythm	110/7305	210/18723	5.40e-05	4.48e-04	110
GO:000974320	Oral cavity	OSCC	response to carbohydrate	128/7305	253/18723	1.11e-04	8.16e-04	128
GO:006082810	Oral cavity	OSCC	regulation of canonical Wnt signaling pathway	128/7305	253/18723	1.11e-04	8.16e-04	128
GO:00103326	Oral cavity	OSCC	response to gamma radiation	36/7305	56/18723	1.12e-04	8.24e-04	36
GO:006161417	Oral cavity	OSCC	pri-miRNA transcription by RNA polymerase II	35/7305	55/18723	1.88e-04	1.27e-03	35
GO:00192214	Oral cavity	OSCC	cytokine-mediated signaling pathway	222/7305	472/18723	2.02e-04	1.35e-03	222
GO:003428420	Oral cavity	OSCC	response to monosaccharide	114/7305	225/18723	2.37e-04	1.54e-03	114
GO:00300983	Oral cavity	OSCC	lymphocyte differentiation	179/7305	374/18723	2.74e-04	1.74e-03	179
GO:006007010	Oral cavity	OSCC	canonical Wnt signaling pathway	148/7305	303/18723	2.89e-04	1.82e-03	148
GO:190289317	Oral cavity	OSCC	regulation of pri-miRNA transcription by RNA polymerase II	34/7305	54/18723	3.12e-04	1.94e-03	34
GO:00169253	Oral cavity	OSCC	protein sumoylation	33/7305	53/18723	5.11e-04	2.98e-03	33
GO:00066945	Oral cavity	OSCC	steroid biosynthetic process	89/7305	173/18723	5.77e-04	3.30e-03	89
GO:00302175	Oral cavity	OSCC	T cell differentiation	126/7305	257/18723	6.51e-04	3.66e-03	126
GO:00329229	Oral cavity	OSCC	circadian regulation of gene expression	40/7305	68/18723	7.28e-04	3.98e-03	40
GO:000974619	Oral cavity	OSCC	response to hexose	109/7305	219/18723	7.41e-04	4.05e-03	109
GO:00614183	Oral cavity	OSCC	regulation of transcription from RNA polymerase II promoter in response to hypoxia	11/7305	13/18723	1.02e-03	5.29e-03	11

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0502016	Breast	Precancer	Prion disease	95/684	273/8465	1.39e-37	1.46e-35	1.12e-35	95
hsa0516618	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0502017	Breast	Precancer	Prion disease	95/684	273/8465	1.39e-37	1.46e-35	1.12e-35	95
hsa0516619	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0502023	Breast	IDC	Prion disease	102/867	273/8465	3.70e-34	4.01e-32	3.00e-32	102
hsa0516624	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0502033	Breast	IDC	Prion disease	102/867	273/8465	3.70e-34	4.01e-32	3.00e-32	102
hsa0516634	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0502043	Breast	DCIS	Prion disease	100/846	273/8465	1.44e-33	1.55e-31	1.14e-31	100
hsa0516642	Breast	DCIS	Human T-cell leukemia virus 1 infection	41/846	222/8465	7.03e-05	6.88e-04	5.07e-04	41
hsa0502053	Breast	DCIS	Prion disease	100/846	273/8465	1.44e-33	1.55e-31	1.14e-31	100
hsa0516652	Breast	DCIS	Human T-cell leukemia virus 1 infection	41/846	222/8465	7.03e-05	6.88e-04	5.07e-04	41
hsa0502018	Cervix	CC	Prion disease	98/1267	273/8465	2.64e-18	1.42e-16	8.42e-17	98
hsa0516620	Cervix	CC	Human T-cell leukemia virus 1 infection	61/1267	222/8465	8.13e-07	7.98e-06	4.72e-06	61
hsa0491212	Cervix	CC	GnRH signaling pathway	26/1267	93/8465	8.72e-04	3.87e-03	2.29e-03	26
hsa0492812	Cervix	CC	Parathyroid hormone synthesis, secretion and action	27/1267	106/8465	3.12e-03	1.19e-02	7.03e-03	27
hsa049336	Cervix	CC	AGE-RAGE signaling pathway in diabetic complications	25/1267	100/8465	5.64e-03	1.88e-02	1.11e-02	25
hsa0502019	Cervix	CC	Prion disease	98/1267	273/8465	2.64e-18	1.42e-16	8.42e-17	98
hsa05166110	Cervix	CC	Human T-cell leukemia virus 1 infection	61/1267	222/8465	8.13e-07	7.98e-06	4.72e-06	61
hsa0491213	Cervix	CC	GnRH signaling pathway	26/1267	93/8465	8.72e-04	3.87e-03	2.29e-03	26

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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
EGR1	CD8TRM	Cervix	N_HPV	EGR3,FOSB,FOS, etc.	2.86e-01
EGR1	ABS	Colorectum	MSI-H	FOS,JUNB,BTG2, etc.	2.58e-01
EGR1	STM	Oral cavity	NEOLP	FOS,JUNB,FOSB, etc.	8.16e-01
EGR1	DUCT1	Pancreas	PanIN	IER2,JUN,FOS, etc.	2.87e-01
EGR1	MAST	Pancreas	ADJ	FOS,FOSB,NFKBIA, etc.	1.53e-01
EGR1	MAST	Pancreas	Healthy	FOS,FOSB,NFKBIA, etc.	9.35e-02
EGR1	MAST	Pancreas	PDAC	FOS,FOSB,NFKBIA, etc.	1.74e-01
EGR1	CHIEF	Stomach	CAG	FOSB,FOS,JUNB, etc.	1.07e-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

EGR1

SNV

Missense_Mutation

c.1145A>G

p.His382Arg

p.H382R

P18146

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

EGR1

insertion

Frame_Shift_Ins

novel

c.358_359insCCGTGATCCTTGGCCGTGGATGTCCCGGCAGCCCGGGTTTGGG

p.Ser120ThrfsTer110

p.S120Tfs*110

P18146

protein_coding

TCGA-A8-A093-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

EGR1

insertion

Frame_Shift_Ins

rs746692720

c.993_994insC

p.His334ProfsTer13

p.H334Pfs*13

P18146

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EGR1

SNV

Missense_Mutation

novel

c.1258N>T

p.Arg420Trp

p.R420W

P18146

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

EGR1

SNV

Missense_Mutation

c.62G>A

p.Gly21Glu

p.G21E

P18146

protein_coding

deleterious_low_confidence(0.01)

benign(0.186)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

EGR1

SNV

Missense_Mutation

c.1055C>T

p.Ser352Phe

p.S352F

P18146

protein_coding

deleterious(0)

probably_damaging(0.916)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

EGR1

SNV

Missense_Mutation

novel

c.1070G>T

p.Arg357Leu

p.R357L

P18146

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-EK-A2R9-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

EGR1

SNV

Missense_Mutation

novel

c.114N>A

p.Met38Ile

p.M38I

P18146

protein_coding

tolerated_low_confidence(0.1)

benign(0.015)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

EGR1

SNV

Missense_Mutation

novel

c.931T>C

p.Tyr311His

p.Y311H

P18146

protein_coding

tolerated(0.12)

probably_damaging(0.96)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

EGR1

SNV

Missense_Mutation

c.964C>T

p.Arg322Cys

p.R322C

P18146

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AA-3663-01

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
1958	EGR1	NA		GENIPIN	GENIPIN	26283511

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