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: ENAH

Gene summary for ENAH

Gene summary.

Gene information	Species	Human
	Gene symbol	ENAH
	Gene ID	55740
	Gene name	ENAH actin regulator
	Gene Alias	ENA
	Cytomap	1q42.12
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q8N8S7

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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
55740	ENAH	GSM5353237_PA_PR5251_T2_S8_L001	Human	Prostate	Tumor	2.94e-06	7.35e-01	0.1622
55740	ENAH	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	1.89e-02	1.05e-01	0.1575
55740	ENAH	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	8.51e-19	2.25e-02	0.1545
55740	ENAH	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	6.62e-10	1.67e-01	0.1569
55740	ENAH	GSM5353247_PA_PR5269_3_S27_L002	Human	Prostate	Tumor	2.42e-05	1.62e-01	0.1532
55740	ENAH	GSM5353248_PA_PR5269_4_S28_L002	Human	Prostate	Tumor	2.65e-06	3.77e-01	0.1541
55740	ENAH	P1_S1_AK	Human	Skin	AK	7.71e-06	3.71e-01	-0.3399
55740	ENAH	P2_S3_AK	Human	Skin	AK	8.77e-04	2.56e-01	-0.3287
55740	ENAH	P4_S8_cSCC	Human	Skin	cSCC	1.80e-08	2.01e-01	-0.3095
55740	ENAH	P5_S10_cSCC	Human	Skin	cSCC	9.56e-32	6.73e-01	-0.299
55740	ENAH	P1_cSCC	Human	Skin	cSCC	1.07e-36	1.41e+00	0.0292
55740	ENAH	P2_cSCC	Human	Skin	cSCC	7.78e-12	5.97e-01	-0.024
55740	ENAH	P4_cSCC	Human	Skin	cSCC	1.55e-30	9.14e-01	-0.00290000000000005
55740	ENAH	P10_cSCC	Human	Skin	cSCC	1.03e-40	1.47e+00	0.1017
55740	ENAH	cSCC_p8	Human	Skin	cSCC	2.26e-02	4.80e-03	-0.1971
55740	ENAH	male-WTA	Human	Thyroid	PTC	1.31e-17	1.67e-01	0.1037
55740	ENAH	PTC01	Human	Thyroid	PTC	7.14e-07	1.50e-01	0.1899
55740	ENAH	PTC03	Human	Thyroid	PTC	2.44e-03	2.10e-01	0.1784
55740	ENAH	PTC04	Human	Thyroid	PTC	2.60e-15	3.43e-01	0.1927
55740	ENAH	PTC05	Human	Thyroid	PTC	7.78e-15	6.86e-01	0.2065

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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
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:00070159	Breast	Precancer	actin filament organization	44/1080	442/18723	3.02e-04	4.35e-03	44
GO:000701514	Breast	IDC	actin filament organization	55/1434	442/18723	2.45e-04	3.84e-03	55
GO:000701524	Breast	DCIS	actin filament organization	56/1390	442/18723	5.90e-05	1.19e-03	56
GO:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:00081549	Cervix	CC	actin polymerization or depolymerization	51/2311	218/18723	4.05e-06	1.05e-04	51
GO:00615647	Cervix	CC	axon development	89/2311	467/18723	1.71e-05	3.27e-04	89
GO:00074097	Cervix	CC	axonogenesis	78/2311	418/18723	1.14e-04	1.43e-03	78
GO:000701516	Endometrium	AEH	actin filament organization	98/2100	442/18723	1.99e-11	2.98e-09	98
GO:00074098	Endometrium	AEH	axonogenesis	81/2100	418/18723	5.54e-07	2.12e-05	81
GO:00615648	Endometrium	AEH	axon development	88/2100	467/18723	6.39e-07	2.38e-05	88
GO:000815410	Endometrium	AEH	actin polymerization or depolymerization	44/2100	218/18723	7.64e-05	1.15e-03	44
GO:000701517	Endometrium	EEC	actin filament organization	95/2168	442/18723	1.31e-09	1.09e-07	95
GO:006156412	Endometrium	EEC	axon development	93/2168	467/18723	9.60e-08	4.69e-06	93
GO:000740912	Endometrium	EEC	axonogenesis	82/2168	418/18723	1.03e-06	3.49e-05	82
GO:000815415	Endometrium	EEC	actin polymerization or depolymerization	44/2168	218/18723	1.59e-04	2.00e-03	44
GO:000701527	Esophagus	ESCC	actin filament organization	259/8552	442/18723	2.37e-08	4.50e-07	259
GO:000815420	Esophagus	ESCC	actin polymerization or depolymerization	130/8552	218/18723	2.19e-05	1.88e-04	130
GO:006156415	Esophagus	ESCC	axon development	251/8552	467/18723	2.41e-04	1.49e-03	251
GO:000740915	Esophagus	ESCC	axonogenesis	219/8552	418/18723	3.14e-03	1.31e-02	219
GO:000701512	Liver	Cirrhotic	actin filament organization	171/4634	442/18723	3.93e-11	2.30e-09	171

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0481014	Breast	IDC	Regulation of actin cytoskeleton	36/867	229/8465	5.79e-03	3.13e-02	2.34e-02	36
hsa0481015	Breast	IDC	Regulation of actin cytoskeleton	36/867	229/8465	5.79e-03	3.13e-02	2.34e-02	36
hsa0481023	Breast	DCIS	Regulation of actin cytoskeleton	35/846	229/8465	6.89e-03	3.37e-02	2.48e-02	35
hsa0481033	Breast	DCIS	Regulation of actin cytoskeleton	35/846	229/8465	6.89e-03	3.37e-02	2.48e-02	35
hsa0481016	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa0401512	Cervix	CC	Rap1 signaling pathway	56/1267	210/8465	6.23e-06	5.61e-05	3.32e-05	56
hsa043609	Cervix	CC	Axon guidance	47/1267	182/8465	8.13e-05	5.38e-04	3.18e-04	47
hsa0481017	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa0401513	Cervix	CC	Rap1 signaling pathway	56/1267	210/8465	6.23e-06	5.61e-05	3.32e-05	56
hsa0436012	Cervix	CC	Axon guidance	47/1267	182/8465	8.13e-05	5.38e-04	3.18e-04	47
hsa0401514	Endometrium	AEH	Rap1 signaling pathway	49/1197	210/8465	2.03e-04	1.78e-03	1.30e-03	49
hsa0481018	Endometrium	AEH	Regulation of actin cytoskeleton	50/1197	229/8465	9.08e-04	5.78e-03	4.23e-03	50
hsa0436010	Endometrium	AEH	Axon guidance	39/1197	182/8465	4.47e-03	2.46e-02	1.80e-02	39
hsa0401515	Endometrium	AEH	Rap1 signaling pathway	49/1197	210/8465	2.03e-04	1.78e-03	1.30e-03	49
hsa0481019	Endometrium	AEH	Regulation of actin cytoskeleton	50/1197	229/8465	9.08e-04	5.78e-03	4.23e-03	50
hsa0436013	Endometrium	AEH	Axon guidance	39/1197	182/8465	4.47e-03	2.46e-02	1.80e-02	39
hsa0401522	Endometrium	EEC	Rap1 signaling pathway	49/1237	210/8465	4.45e-04	3.47e-03	2.59e-03	49
hsa0481024	Endometrium	EEC	Regulation of actin cytoskeleton	49/1237	229/8465	3.20e-03	1.78e-02	1.33e-02	49
hsa0436022	Endometrium	EEC	Axon guidance	39/1237	182/8465	7.78e-03	3.66e-02	2.73e-02	39
hsa0401532	Endometrium	EEC	Rap1 signaling pathway	49/1237	210/8465	4.45e-04	3.47e-03	2.59e-03	49

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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

ENAH

SNV

Missense_Mutation

novel

c.599N>C

p.Arg200Pro

p.R200P

Q8N8S7

protein_coding

tolerated_low_confidence(0.25)

benign(0.226)

TCGA-A2-A3XX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ENAH

SNV

Missense_Mutation

novel

c.678N>T

p.Arg226Ser

p.R226S

Q8N8S7

protein_coding

deleterious_low_confidence(0.04)

benign(0)

TCGA-A8-A06P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

ENAH

SNV

Missense_Mutation

c.1268C>A

p.Ser423Tyr

p.S423Y

Q8N8S7

protein_coding

deleterious(0.01)

possibly_damaging(0.898)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ENAH

SNV

Missense_Mutation

c.292A>G

p.Asn98Asp

p.N98D

Q8N8S7

protein_coding

deleterious(0)

probably_damaging(0.917)

TCGA-AR-A1AH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

ENAH

SNV

Missense_Mutation

c.1169N>T

p.Thr390Ile

p.T390I

Q8N8S7

protein_coding

deleterious(0)

probably_damaging(0.968)

TCGA-E9-A1R5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ENAH

SNV

Missense_Mutation

c.1312N>T

p.Pro438Ser

p.P438S

Q8N8S7

protein_coding

tolerated(0.27)

probably_damaging(0.982)

TCGA-S3-AA10-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

ENAH

deletion

Frame_Shift_Del

novel

c.673delG

p.Glu225ArgfsTer27

p.E225Rfs*27

Q8N8S7

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ENAH

SNV

Missense_Mutation

rs549324711

c.1450G>A

p.Ala484Thr

p.A484T

Q8N8S7

protein_coding

tolerated(0.07)

benign(0.074)

TCGA-C5-A1M7-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ENAH

SNV

Missense_Mutation

c.1432N>A

p.Glu478Lys

p.E478K

Q8N8S7

protein_coding

deleterious(0.01)

probably_damaging(0.941)

TCGA-EK-A3GJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ENAH

SNV

Missense_Mutation

novel

c.256N>C

p.Val86Leu

p.V86L

Q8N8S7

protein_coding

deleterious(0)

possibly_damaging(0.844)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

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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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