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	LZE5T	Human	Esophagus	ESCC	3.67e-02	5.61e-01	0.0514
2029	ENSA	LZE7T	Human	Esophagus	ESCC	6.30e-12	1.38e+00	0.0667
2029	ENSA	LZE8T	Human	Esophagus	ESCC	3.45e-09	5.87e-01	0.067
2029	ENSA	LZE20T	Human	Esophagus	ESCC	2.93e-03	5.30e-01	0.0662
2029	ENSA	LZE22D1	Human	Esophagus	HGIN	7.43e-03	3.90e-01	0.0595
2029	ENSA	LZE24T	Human	Esophagus	ESCC	3.89e-28	1.25e+00	0.0596
2029	ENSA	LZE21T	Human	Esophagus	ESCC	1.54e-02	7.56e-01	0.0655
2029	ENSA	LZE6T	Human	Esophagus	ESCC	3.77e-08	7.89e-01	0.0845
2029	ENSA	P1T-E	Human	Esophagus	ESCC	8.28e-18	1.28e+00	0.0875
2029	ENSA	P2T-E	Human	Esophagus	ESCC	3.78e-87	1.80e+00	0.1177
2029	ENSA	P4T-E	Human	Esophagus	ESCC	1.44e-38	1.22e+00	0.1323
2029	ENSA	P5T-E	Human	Esophagus	ESCC	7.85e-39	1.09e+00	0.1327
2029	ENSA	P8T-E	Human	Esophagus	ESCC	9.60e-35	8.14e-01	0.0889
2029	ENSA	P9T-E	Human	Esophagus	ESCC	9.09e-42	1.52e+00	0.1131
2029	ENSA	P10T-E	Human	Esophagus	ESCC	4.56e-56	1.30e+00	0.116
2029	ENSA	P11T-E	Human	Esophagus	ESCC	6.16e-18	1.52e+00	0.1426
2029	ENSA	P12T-E	Human	Esophagus	ESCC	9.47e-50	1.01e+00	0.1122
2029	ENSA	P15T-E	Human	Esophagus	ESCC	5.57e-45	1.39e+00	0.1149
2029	ENSA	P16T-E	Human	Esophagus	ESCC	1.61e-39	9.01e-01	0.1153
2029	ENSA	P17T-E	Human	Esophagus	ESCC	3.12e-16	1.18e+00	0.1278

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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:00342849	Breast	Precancer	response to monosaccharide	29/1080	225/18723	4.19e-05	9.00e-04	29
GO:00097439	Breast	Precancer	response to carbohydrate	31/1080	253/18723	6.15e-05	1.25e-03	31
GO:00097469	Breast	Precancer	response to hexose	27/1080	219/18723	1.61e-04	2.69e-03	27
GO:00316679	Breast	Precancer	response to nutrient levels	47/1080	474/18723	2.09e-04	3.27e-03	47
GO:00097498	Breast	Precancer	response to glucose	25/1080	212/18723	5.46e-04	7.00e-03	25
GO:00353049	Breast	Precancer	regulation of protein dephosphorylation	14/1080	90/18723	6.16e-04	7.72e-03	14
GO:00507086	Breast	Precancer	regulation of protein secretion	28/1080	268/18723	1.76e-03	1.74e-02	28
GO:00158336	Breast	Precancer	peptide transport	27/1080	264/18723	2.84e-03	2.49e-02	27
GO:00353086	Breast	Precancer	negative regulation of protein dephosphorylation	7/1080	34/18723	2.84e-03	2.49e-02	7
GO:00900875	Breast	Precancer	regulation of peptide transport	22/1080	202/18723	3.14e-03	2.65e-02	22
GO:00300736	Breast	Precancer	insulin secretion	21/1080	195/18723	4.38e-03	3.42e-02	21
GO:00716926	Breast	Precancer	protein localization to extracellular region	34/1080	368/18723	4.65e-03	3.58e-02	34
GO:00075845	Breast	Precancer	response to nutrient	19/1080	174/18723	5.63e-03	4.08e-02	19
GO:00093067	Breast	Precancer	protein secretion	33/1080	359/18723	5.65e-03	4.08e-02	33
GO:00027915	Breast	Precancer	regulation of peptide secretion	21/1080	200/18723	5.86e-03	4.20e-02	21
GO:00355927	Breast	Precancer	establishment of protein localization to extracellular region	33/1080	360/18723	5.89e-03	4.21e-02	33
GO:00027904	Breast	Precancer	peptide secretion	24/1080	242/18723	6.87e-03	4.67e-02	24
GO:00507966	Breast	Precancer	regulation of insulin secretion	18/1080	165/18723	6.99e-03	4.71e-02	18
GO:003428414	Breast	IDC	response to monosaccharide	36/1434	225/18723	1.94e-05	4.83e-04	36
GO:003166714	Breast	IDC	response to nutrient levels	62/1434	474/18723	2.33e-05	5.57e-04	62

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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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