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: ENSA

Gene summary for ENSA

Gene summary.

Gene information	Species	Human
	Gene symbol	ENSA
	Gene ID	2029
	Gene name	endosulfine alpha
	Gene Alias	ARPP-19e
	Cytomap	1q21.3
	Gene Type	protein-coding
	GO ID	GO:0000086
	UniProtAcc	O43768

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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
2029	ENSA	GSM4909285	Human	Breast	IDC	1.42e-02	2.52e-01	0.21
2029	ENSA	GSM4909286	Human	Breast	IDC	3.47e-03	-9.54e-02	0.1081
2029	ENSA	GSM4909288	Human	Breast	IDC	3.33e-03	-1.63e-01	0.0988
2029	ENSA	GSM4909294	Human	Breast	IDC	2.99e-02	2.13e-01	0.2022
2029	ENSA	GSM4909296	Human	Breast	IDC	2.18e-10	9.28e-02	0.1524
2029	ENSA	GSM4909297	Human	Breast	IDC	1.40e-18	1.19e-02	0.1517
2029	ENSA	GSM4909301	Human	Breast	IDC	8.60e-56	8.71e-01	0.1577
2029	ENSA	GSM4909302	Human	Breast	IDC	1.20e-05	1.73e-01	0.1545
2029	ENSA	GSM4909306	Human	Breast	IDC	1.01e-09	4.72e-01	0.1564
2029	ENSA	GSM4909307	Human	Breast	IDC	9.42e-21	5.73e-01	0.1569
2029	ENSA	GSM4909308	Human	Breast	IDC	3.51e-76	9.51e-01	0.158
2029	ENSA	GSM4909309	Human	Breast	IDC	4.08e-04	-1.44e-01	0.0483
2029	ENSA	GSM4909311	Human	Breast	IDC	1.29e-31	-4.03e-01	0.1534
2029	ENSA	GSM4909312	Human	Breast	IDC	2.29e-12	1.66e-01	0.1552
2029	ENSA	GSM4909313	Human	Breast	IDC	1.40e-07	1.20e-01	0.0391
2029	ENSA	GSM4909316	Human	Breast	IDC	7.18e-17	4.79e-01	0.21
2029	ENSA	GSM4909318	Human	Breast	IDC	1.56e-07	3.96e-01	0.2031
2029	ENSA	GSM4909319	Human	Breast	IDC	8.44e-45	-8.28e-02	0.1563
2029	ENSA	GSM4909320	Human	Breast	IDC	6.20e-08	-3.78e-01	0.1575
2029	ENSA	GSM4909321	Human	Breast	IDC	1.44e-24	3.58e-01	0.1559

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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
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
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:004593623	Lung	AAH	negative regulation of phosphate metabolic process	28/613	441/18723	6.88e-04	2.54e-02	28
GO:001056323	Lung	AAH	negative regulation of phosphorus metabolic process	28/613	442/18723	7.12e-04	2.55e-02	28
GO:000974323	Lung	AAH	response to carbohydrate	18/613	253/18723	1.76e-03	4.22e-02	18
GO:00447728	Oral cavity	OSCC	mitotic cell cycle phase transition	255/7305	424/18723	5.29e-19	6.98e-17	255
GO:001056320	Oral cavity	OSCC	negative regulation of phosphorus metabolic process	246/7305	442/18723	6.12e-13	2.89e-11	246
GO:004593620	Oral cavity	OSCC	negative regulation of phosphate metabolic process	245/7305	441/18723	8.85e-13	4.09e-11	245
GO:000647015	Oral cavity	OSCC	protein dephosphorylation	162/7305	281/18723	1.56e-10	4.56e-09	162
GO:00163119	Oral cavity	OSCC	dephosphorylation	220/7305	417/18723	6.33e-09	1.34e-07	220
GO:003166720	Oral cavity	OSCC	response to nutrient levels	245/7305	474/18723	1.02e-08	2.10e-07	245
GO:003530319	Oral cavity	OSCC	regulation of dephosphorylation	80/7305	128/18723	6.10e-08	1.10e-06	80
GO:003530420	Oral cavity	OSCC	regulation of protein dephosphorylation	60/7305	90/18723	9.75e-08	1.67e-06	60
GO:00000863	Oral cavity	OSCC	G2/M transition of mitotic cell cycle	84/7305	137/18723	9.99e-08	1.70e-06	84
GO:00448393	Oral cavity	OSCC	cell cycle G2/M phase transition	89/7305	148/18723	1.51e-07	2.51e-06	89
GO:00075849	Oral cavity	OSCC	response to nutrient	95/7305	174/18723	2.09e-05	1.99e-04	95
GO:000974320	Oral cavity	OSCC	response to carbohydrate	128/7305	253/18723	1.11e-04	8.16e-04	128
GO:003428420	Oral cavity	OSCC	response to monosaccharide	114/7305	225/18723	2.37e-04	1.54e-03	114
GO:000974619	Oral cavity	OSCC	response to hexose	109/7305	219/18723	7.41e-04	4.05e-03	109
GO:000930610	Oral cavity	OSCC	protein secretion	169/7305	359/18723	1.04e-03	5.34e-03	169
GO:000974917	Oral cavity	OSCC	response to glucose	105/7305	212/18723	1.13e-03	5.78e-03	105
GO:003559210	Oral cavity	OSCC	establishment of protein localization to extracellular region	169/7305	360/18723	1.21e-03	6.08e-03	169

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

ENSA

SNV

Missense_Mutation

c.5N>A

p.Ser2Tyr

p.S2Y

O43768

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.989)

TCGA-A2-A04U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ENSA

SNV

Missense_Mutation

c.109N>G

p.Leu37Val

p.L37V

O43768

protein_coding

deleterious(0.05)

probably_damaging(0.962)

TCGA-B6-A0IB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ENSA

insertion

Frame_Shift_Ins

novel

c.181_182insTGGTTAGGGAGGGAGAG

p.Gly61ValfsTer39

p.G61Vfs*39

O43768

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ENSA

SNV

Missense_Mutation

novel

c.24G>T

p.Glu8Asp

p.E8D

O43768

protein_coding

tolerated(0.15)

benign(0.009)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

ENSA

insertion

Frame_Shift_Ins

novel

c.347_348insC

p.Gln117ThrfsTer21

p.Q117Tfs*21

O43768

protein_coding

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

ENSA

SNV

Missense_Mutation

c.301N>A

p.Ala101Thr

p.A101T

O43768

protein_coding

tolerated(0.13)

possibly_damaging(0.692)

TCGA-AX-A06D-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

carboplatin

ENSA

SNV

Missense_Mutation

c.301N>A

p.Ala101Thr

p.A101T

O43768

protein_coding

tolerated(0.13)

possibly_damaging(0.692)

TCGA-AX-A06H-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

ENSA

SNV

Missense_Mutation

novel

c.266C>T

p.Ala89Val

p.A89V

O43768

protein_coding

deleterious(0.03)

benign(0.27)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

ENSA

SNV

Missense_Mutation

rs759538315

c.154G>A

p.Asp52Asn

p.D52N

O43768

protein_coding

tolerated(0.14)

benign(0.07)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ENSA

SNV

Missense_Mutation

novel

c.24N>T

p.Glu8Asp

p.E8D

O43768

protein_coding

tolerated(0.15)

benign(0.009)

TCGA-BK-A6W3-01

Endometrium

uterine corpus endometrioid 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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